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Logo of actae2this articlesearchopen accesssubmitActa Crystallographica Section E: Crystallographic CommunicationsActa Crystallographica Section E: Crystallographic Communications
 
Acta Crystallogr E Crystallogr Commun. 2017 April 1; 73(Pt 4): 503–506.
Published online 2017 March 14. doi:  10.1107/S2056989017003607
PMCID: PMC5382608

Crystal structure of methyl (4R)-4-(4-meth­oxy­benzo­yl)-4-{[(1R)-1-phenyl­eth­yl]carbamo­yl}butano­ate

Abstract

The title compound, C22H25NO5, was prepared by CAN [cerium(IV) ammonium nitrate] oxidation of the corresponding β-lactam. The dihedral angle between the benzene rings is 13.3 (4)° and the C—N—C(=O)—C torsion angle is 176.1 (6)°. In the crystal, amide-C(4) N—H(...)O and reinforcing C—H(...)O hydrogen bonds link the mol­ecules into infinite [010] chains. Further C—H(...)O hydrogen bonds cross-link the chains in the c-axis direction.

Keywords: crystal structure, hydrogen bonds, CAN oxidation, β-lactame, glutarate

Chemical context  

Cerium(IV) ammonium nitrate (CAN) is a powerful reagent in organic synthesis, which promotes a wide range of reactions that go well beyond its usual role as an oxidant (Sridharan & Menendez, 2010  ). Chemoselective mono-de­benzyl­ation of benzyl tertiary amines occurs in the presence of N-benzyl amides, O-benzyl ethers and esters (Bull et al., 2000  ); inter­estingly this reaction can be applied to mono-de­benzyl­ation of β-amino esters as a way to obtain β-lactams (Davies & Ichihara, 1998  ) or piperidone (Garrido et al., 2011  ), providing as well a new oxidative methodology as catch linker for reaction monitoring and optimization on solid phase support (Davies et al., 2008  ). Our group has demonstrated two different domino reactions, one by lithium amide addition to diendioate that can be applied to the synthesis of cyclo­penta­nic (Urones et al., 2004  ) or cyclo­hexa­nic (Garrido et al., 2006  ) derivatives and the other by addition to Baylis–Hillman (Garrido et al., 2008  ) derivatives with application to the synthesis of non-peptidic neurokinin NK1 receptor antagonist (+)-L-733,060 (Garrido et al., 2010  ). Within this context of the synthesis of biologically active compounds, we are inter­ested in the synthesis of β-lactam and its mono-deprotection, as shown in the Scheme, where the asymmetric 4-benzoyl glutarate is readily obtained by CAN oxidation of the appropriate substituted β-lactam. For the CAN oxidation reaction of a related trialkyl amine derivative providing monodeprotection, see Garrido et al. (2011  ).

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Object name is e-73-00503-scheme1.jpg

Structural commentary  

The mol­ecular structure of the title compound is shown in Fig. 1  . The mol­ecule consists of an ester amide glutarate derivative with a p-metoxybenzoyl group as substituent: all the bond lengths and angles are within normal ranges. The almost planar conformation of the ester group is established from the torsion angle C20—C21—O4—C22 of 178.6 (3)°. The ether group atom C1 and the carbonyl group atom C8 are almost coplanar with the benzene ring, the C7—O1—C1—C6 and O2—C8—C4—C5 torsion angles being 177.9 (1) and 172.4 (8)°, respectively. The C11 methyl group is also almost coplanar with the its benzene ring, as indicated by the torsion angle C18—C11—C12—C13 of 176.68 (7)°. The dihedral angle between the aromatic rings is 13.3 (4)°.

Figure 1
The mol­ecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radius.

Supra­molecular features  

In the extended structure of the title compound, hydrogen bonds are one of the primary factors in building the crystal network (Table 1  ). Inter­molecular N1—H1(...)O3i (dotted light-blue lines), C9—H9(...)O3i dotted (orange lines) and C20—H20A(...)O2i (dotted blue lines) hydrogen bonds link neighboring mol­ecules, generating infinite chains running along the b-axis direction (Fig. 2  ). These chains are joined to each other along c axis by C17—H17(...)O5ii inter­actions (dotted pink lines), as shown in Fig. 3  . The packing viewed along the [010] direction is illustrated in Fig. 4  .

Figure 2
A view of the C20—H20A(...)O2 (dotted blue lines), N1—H1(...)O3 (dotted light-blue lines) and C9—H9(...)O3 (dotted orange lines) hydrogen bonds (see Table 1  ), which link the mol­ecules into ...
Figure 3
A view of the C17—H17(...)O5 (dotted pink lines) hydrogen bonds in the extended structure of the title compound.
Figure 4
Crystal packing of the title compound, viewed along the [010] direction.
Table 1
Hydrogen-bond geometry (Å, °)

Synthesis and crystallization  

(3S,4SR)-N-(α-methyl­benz­yl)-4-(para-meth­oxy­phen­yl)-3-meth­oxy­carbonyl­ethyl-β-lactam (I) (26.50 mg, 76.12 µmol) was dissolved in 12.00 ml of a mixture of MeCN–H2O (5:1) and CAN (150.1 mg, 0.27 mmol) was added and allowed to stir for 15 minutes under an argon atmosphere. Solid NaHCO3 was then added and the mixture allowed to stir for another 15 minutes. It was filtered over celite, washed with EtOAc and NaHSO4 and the phases separated. The organic phase was treated with H2O, brine and anhydrous Na2SO4, filtered and the solvent removed under reduced pressure to obtained the crude product (23.4 mg), which was purified by flash chromatography (silica gel, hexa­ne/EtOAC 7:3) and crystallized from hexa­ne/EtOAc solution to yield 7.7 mg of product (II) (28%), m.p. 440.6 K.

IR (film): 700, 802, 1026, 1171, 1260, 1373, 1456, 1512, 1601, 1736, 2849, 2918, 3333. 1H NMR (200 MHz, CDCl3) δ 8.33–7.78 (m, 2H, Ar), 7.48–7.25 (m, 5H, Ar), 6.99–6.81 (m, 2H, Ar), 5.05 (1H, quint, J = 6.9 Hz), 4.65 (1H, t, J = 5.5 Hz), 3.87 (s, 3H, COOMe), 3.65 (s, 3H, OMe), 2.50–2.20 (m, 4H), 1.47 (3H, d, J = 6.9 Hz, CH3).13C NMR (50 MHz, CDCl3) δ 193.4 (C, C=O), 169.4(C, C=O), 164.1 (C, Cipso), 160.6 (C, Cipso), 139.2(C, Cipso), 127.5 (CH × 2, Ar), 125.0 (CH × 2, Ar), 122.3 (CH, Ar), 122.1 (CH × 2, Ar), 110.4 (CH × 2, Ar), 51.9 (CH3, COOMe), 50.1 (CH), 48.1 (CH3, OMe), 45.3 (CH), 27.6 (CH2), 23.3 (CH2), 18.4 (CH3). HRMS (EI): C22H26NO5 requires (M + H)+, 384.1803, found 384.1805.

Refinement  

Crystal data, data collection and structure refinement details are summarized in Table 2  . The hydrogen atoms were positioned geometrically, with C–H distances constrained to 0.93 Å (aromatic CH), 0.97 Å (methyl­ene CH2), 0.98 methyne CH) and N—H = 0.86 Å (amine), and refined using a riding model with U iso(H) = 1.2 or 1.5U eq(C,N).

Table 2
Experimental details

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989017003607/hb7652sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989017003607/hb7652Isup2.hkl

CCDC reference: 1524270

Additional supporting information: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors gratefully acknowledge the help of A. Lithgow (NMR) and C. Raposo (MS) of the Universidad de Salamanca.

supplementary crystallographic information

Crystal data

C22H25NO5F(000) = 816
Mr = 383.43Dx = 1.242 Mg m3
Orthorhombic, P212121Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ac 2abCell parameters from 3001 reflections
a = 23.739 (3) Åθ = 3.1–60.0°
b = 4.7791 (5) ŵ = 0.72 mm1
c = 18.0722 (19) ÅT = 298 K
V = 2050.3 (4) Å3Prismatic, colorless
Z = 40.12 × 0.10 × 0.08 mm

Data collection

Bruker APEXII CCD area-detector diffractometer2913 independent reflections
Radiation source: fine-focus sealed tube1854 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.053
phi and ω scansθmax = 66.3°, θmin = 3.1°
Absorption correction: multi-scan (SADABS; Bruker, 2006)h = −26→27
Tmin = 0.917, Tmax = 0.944k = −5→4
9316 measured reflectionsl = −18→21

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.067Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.163H-atom parameters constrained
S = 1.25w = 1/[σ2(Fo2) + (0.0115P)2 + 2.2937P] where P = (Fo2 + 2Fc2)/3
2913 reflections(Δ/σ)max < 0.001
256 parametersΔρmax = 0.15 e Å3
0 restraintsΔρmin = −0.19 e Å3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O10.14092 (19)0.5853 (12)0.7501 (3)0.0968 (16)
O2−0.07814 (19)0.4116 (10)0.9431 (2)0.0873 (15)
O30.0203 (2)0.3173 (8)1.0773 (3)0.0954 (17)
O4−0.2138 (2)1.1081 (15)1.0782 (4)0.135 (2)
O5−0.1868 (3)0.7840 (19)1.1507 (4)0.172 (4)
N10.0500 (2)0.7476 (10)1.1092 (3)0.0660 (15)
H10.04570.92431.10220.079*
C10.0970 (3)0.5689 (16)0.7980 (4)0.0737 (19)
C20.0521 (3)0.3913 (14)0.7891 (4)0.077 (2)
H20.05030.27120.74870.093*
C30.0090 (3)0.3946 (15)0.8420 (4)0.0721 (19)
H3−0.02160.27540.83590.087*
C40.0105 (3)0.5687 (13)0.9029 (4)0.0620 (16)
C50.0563 (3)0.7466 (14)0.9097 (4)0.0742 (19)
H50.05840.86730.95000.089*
C60.0987 (3)0.7474 (16)0.8579 (4)0.081 (2)
H60.12880.86990.86320.098*
C70.1414 (3)0.3946 (19)0.6885 (5)0.116 (3)
H7A0.13990.20570.70650.173*
H7B0.17540.42070.66050.173*
H7C0.10940.43020.65750.173*
C8−0.0366 (3)0.5519 (12)0.9563 (4)0.0622 (16)
C9−0.0306 (2)0.7072 (11)1.0286 (3)0.0621 (17)
H9−0.02050.90191.01800.075*
C100.0160 (3)0.5753 (13)1.0744 (4)0.0628 (16)
C110.0948 (3)0.6560 (14)1.1592 (4)0.077 (2)
H110.10050.45531.15080.093*
C120.1492 (3)0.8035 (14)1.1383 (4)0.0658 (18)
C130.1712 (4)0.7725 (19)1.0682 (5)0.106 (3)
H130.15230.66231.03390.127*
C140.2205 (4)0.901 (3)1.0482 (5)0.128 (4)
H140.23500.87611.00090.154*
C150.2483 (4)1.065 (2)1.0980 (7)0.120 (3)
H150.28171.15331.08450.144*
C160.2273 (4)1.100 (2)1.1666 (6)0.118 (3)
H160.24651.21031.20060.142*
C170.1779 (3)0.9729 (15)1.1865 (4)0.085 (2)
H170.16351.00221.23370.102*
C180.0765 (3)0.692 (2)1.2385 (4)0.117 (3)
H18A0.07120.88781.24870.176*
H18B0.10490.61811.27080.176*
H18C0.04170.59461.24640.176*
C19−0.0847 (2)0.7043 (12)1.0759 (3)0.0672 (17)
H19A−0.09690.51201.08210.081*
H19B−0.07600.77811.12450.081*
C20−0.1329 (2)0.8718 (15)1.0434 (4)0.078 (2)
H20A−0.11901.05321.02770.093*
H20B−0.14730.77571.00000.093*
C21−0.1799 (3)0.9125 (19)1.0976 (5)0.082 (2)
C22−0.2616 (3)1.157 (2)1.1275 (6)0.162 (5)
H22A−0.27730.98091.14250.243*
H22B−0.28981.26421.10200.243*
H22C−0.24911.25831.17030.243*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.084 (3)0.115 (4)0.091 (4)−0.005 (3)0.004 (3)−0.005 (4)
O20.099 (3)0.090 (3)0.072 (3)−0.043 (3)−0.008 (3)−0.009 (3)
O30.135 (4)0.031 (2)0.120 (5)0.001 (3)−0.050 (4)0.001 (3)
O40.108 (4)0.149 (6)0.149 (6)0.035 (4)0.045 (4)0.051 (5)
O50.159 (6)0.218 (8)0.139 (6)0.052 (6)0.054 (5)0.093 (6)
N10.087 (3)0.034 (3)0.078 (4)0.003 (3)−0.032 (3)0.002 (3)
C10.074 (4)0.068 (4)0.079 (5)0.007 (4)−0.009 (4)0.008 (5)
C20.089 (5)0.064 (5)0.078 (5)−0.001 (4)−0.008 (4)−0.010 (4)
C30.080 (4)0.063 (4)0.073 (5)−0.014 (4)−0.008 (4)−0.002 (4)
C40.072 (4)0.047 (3)0.067 (4)−0.003 (3)−0.013 (3)0.003 (4)
C50.084 (4)0.063 (4)0.076 (5)−0.013 (4)−0.010 (4)−0.007 (4)
C60.078 (4)0.075 (5)0.091 (6)−0.019 (4)−0.009 (4)−0.004 (5)
C70.121 (7)0.126 (7)0.100 (7)0.008 (6)0.018 (5)−0.032 (7)
C80.083 (4)0.042 (3)0.062 (4)−0.012 (3)−0.017 (4)0.000 (3)
C90.077 (4)0.036 (3)0.074 (5)−0.007 (3)−0.018 (3)0.002 (3)
C100.082 (4)0.044 (3)0.063 (4)−0.001 (4)−0.021 (3)−0.001 (4)
C110.094 (5)0.055 (4)0.082 (5)0.005 (4)−0.037 (4)0.006 (4)
C120.074 (4)0.054 (4)0.070 (5)0.012 (3)−0.018 (4)−0.003 (4)
C130.104 (6)0.126 (7)0.088 (7)0.009 (6)−0.010 (5)−0.034 (6)
C140.104 (7)0.195 (12)0.085 (7)0.025 (7)0.013 (5)−0.009 (8)
C150.090 (6)0.139 (9)0.132 (10)0.002 (6)0.003 (7)0.030 (9)
C160.097 (6)0.128 (8)0.128 (9)−0.033 (6)−0.005 (6)−0.018 (8)
C170.092 (5)0.086 (5)0.078 (6)−0.005 (4)0.000 (4)−0.013 (5)
C180.105 (5)0.184 (10)0.063 (5)−0.036 (6)−0.020 (4)0.038 (7)
C190.088 (4)0.054 (4)0.059 (4)−0.006 (3)−0.009 (4)0.007 (4)
C200.077 (4)0.078 (5)0.078 (5)−0.009 (4)−0.006 (4)0.016 (4)
C210.083 (5)0.088 (5)0.075 (6)−0.005 (5)−0.001 (4)0.014 (5)
C220.107 (6)0.185 (11)0.195 (11)0.033 (7)0.073 (7)0.023 (9)

Geometric parameters (Å, º)

O1—C11.357 (8)C9—H90.9800
O1—C71.439 (8)C11—C181.508 (9)
O2—C81.215 (6)C11—C121.518 (9)
O3—C101.238 (6)C11—H110.9800
O4—C211.282 (9)C12—C171.371 (9)
O4—C221.461 (8)C12—C131.379 (10)
O5—C211.151 (8)C13—C141.369 (11)
N1—C101.314 (7)C13—H130.9300
N1—C111.461 (7)C14—C151.364 (12)
N1—H10.8600C14—H140.9300
C1—C21.373 (9)C15—C161.346 (11)
C1—C61.378 (9)C15—H150.9300
C2—C31.398 (8)C16—C171.369 (10)
C2—H20.9300C16—H160.9300
C3—C41.380 (8)C17—H170.9300
C3—H30.9300C18—H18A0.9600
C4—C51.386 (8)C18—H18B0.9600
C4—C81.481 (8)C18—H18C0.9600
C5—C61.374 (9)C19—C201.515 (8)
C5—H50.9300C19—H19A0.9700
C6—H60.9300C19—H19B0.9700
C7—H7A0.9600C20—C211.498 (9)
C7—H7B0.9600C20—H20A0.9700
C7—H7C0.9600C20—H20B0.9700
C8—C91.509 (8)C22—H22A0.9600
C9—C101.519 (8)C22—H22B0.9600
C9—C191.542 (8)C22—H22C0.9600
C1—O1—C7117.6 (6)C12—C11—H11107.4
C21—O4—C22115.9 (7)C17—C12—C13117.3 (7)
C10—N1—C11123.7 (5)C17—C12—C11122.6 (7)
C10—N1—H1118.1C13—C12—C11120.1 (7)
C11—N1—H1118.1C14—C13—C12121.3 (8)
O1—C1—C2123.9 (7)C14—C13—H13119.4
O1—C1—C6116.3 (7)C12—C13—H13119.4
C2—C1—C6119.8 (7)C15—C14—C13119.8 (9)
C1—C2—C3118.7 (7)C15—C14—H14120.1
C1—C2—H2120.6C13—C14—H14120.1
C3—C2—H2120.6C16—C15—C14120.0 (10)
C4—C3—C2122.2 (6)C16—C15—H15120.0
C4—C3—H3118.9C14—C15—H15120.0
C2—C3—H3118.9C15—C16—C17120.3 (9)
C3—C4—C5117.5 (6)C15—C16—H16119.9
C3—C4—C8117.9 (6)C17—C16—H16119.9
C5—C4—C8124.6 (6)C16—C17—C12121.4 (8)
C6—C5—C4121.0 (7)C16—C17—H17119.3
C6—C5—H5119.5C12—C17—H17119.3
C4—C5—H5119.5C11—C18—H18A109.5
C5—C6—C1120.8 (7)C11—C18—H18B109.5
C5—C6—H6119.6H18A—C18—H18B109.5
C1—C6—H6119.6C11—C18—H18C109.5
O1—C7—H7A109.5H18A—C18—H18C109.5
O1—C7—H7B109.5H18B—C18—H18C109.5
H7A—C7—H7B109.5C20—C19—C9114.2 (5)
O1—C7—H7C109.5C20—C19—H19A108.7
H7A—C7—H7C109.5C9—C19—H19A108.7
H7B—C7—H7C109.5C20—C19—H19B108.7
O2—C8—C4121.0 (6)C9—C19—H19B108.7
O2—C8—C9121.2 (6)H19A—C19—H19B107.6
C4—C8—C9117.8 (5)C21—C20—C19112.2 (6)
C8—C9—C10109.7 (5)C21—C20—H20A109.2
C8—C9—C19113.3 (5)C19—C20—H20A109.2
C10—C9—C19107.5 (5)C21—C20—H20B109.2
C8—C9—H9108.7C19—C20—H20B109.2
C10—C9—H9108.7H20A—C20—H20B107.9
C19—C9—H9108.7O5—C21—O4121.9 (9)
O3—C10—N1123.6 (6)O5—C21—C20125.6 (9)
O3—C10—C9119.7 (6)O4—C21—C20112.5 (7)
N1—C10—C9116.7 (5)O4—C22—H22A109.5
N1—C11—C18110.0 (6)O4—C22—H22B109.5
N1—C11—C12109.0 (5)H22A—C22—H22B109.5
C18—C11—C12115.3 (6)O4—C22—H22C109.5
N1—C11—H11107.4H22A—C22—H22C109.5
C18—C11—H11107.4H22B—C22—H22C109.5

Hydrogen-bond geometry (Å, º)

D—H···AD—HH···AD···AD—H···A
N1—H1···O3i0.862.022.871 (6)168
C9—H9···O3i0.982.463.277 (7)141
C20—H20A···O2i0.972.493.410 (8)158
C17—H17···O5ii0.932.553.303 (11)139

Symmetry codes: (i) x, y+1, z; (ii) −x, y+1/2, −z+5/2.

References

  • Bruker (2006). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
  • Bull, S. D., Davies, S. G., Fenton, G., Mulvaney, A. W., Prasad, R. S. & Smith, A. D. (2000). J. Chem. Soc. Perkin Trans. 1, pp. 3765–3774.
  • Davies, S. G. & Ichihara, O. (1998). Tetrahedron Lett. 39, 6045–6048.
  • Davies, S. G., Mortimer, D. A. B., Mulvaney, A., Russell, A. J., Skarphedinsson, H., Smith, A. D. & Vickers, R. J. (2008). Org. Biomol. Chem. 6, 1625–1634. [PubMed]
  • Garrido, N. M., Díez, D., Domínguez, S. H., García, M., Sánchez, M. R. & Davies, S. G. (2006). Tetrahedron Asymmetry, 17, 2183–2186.
  • Garrido, N. M., García, M., Díez, D., Sánchez, M. R., Sanz, F. & Urones, J. G. (2008). Org. Lett. 10, 1687–1690. [PubMed]
  • Garrido, N. M., García, M., Sánchez, M. R., Díez, D. & Urones, J. G. (2010). Synlett, pp. 387–390.
  • Garrido, N. M., Sánchez, M. R., Díez, D., Sanz, F. & Urones, J. G. (2011). Tetrahedron Asymmetry, 22, 872–880.
  • Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.
  • Sheldrick, G. M. (2008). Acta Cryst A64, 112–122. [PubMed]
  • Sridharan, V. & Menéndez, J. C. (2010). Chem. Rev. 110, 3805–3849. [PubMed]
  • Urones, J. G., Garrido, N. M., Díez, D., El Hammoumi, M. M., Dominguez, S. H., Casaseca, J. A., Davies, S. G. & Smith, A. D. (2004). Org. Biomol. Chem. 2, 364–372. [PubMed]

Articles from Acta Crystallographica Section E: Crystallographic Communications are provided here courtesy of International Union of Crystallography