4-Nitrobenzaldehyde → [(E)-(S)-1-benzyl-4-(4-nitro-phenyl)-2-oxo-but-3-enyl]-carbamic acid tert-butyl ester

HRID 889555Notes

Reaction equation

HRID 889555 reaction equation
[C:1]([O:5][C:6](=[O:32])[NH:7][CH:8]([C:16]1NC(=O)C=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=2)[CH:21]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].C[O:34]P(CC(=O)[C@@H](NC(OC(C)(C)C)=O)CC1C=CC=CC=1)(=O)OC.[N+](C1C=CC(C=O)=CC=1)([O-])=O.C(=O)([O-])[O-].[K+].[K+]>C(O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:32])[NH:7][C@@H:8]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:16](=[O:34])/[CH:21]=[CH:20]/[C:22]1[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 5414-NitrobenzaldehydeHCID 11430Potassium CarbonateHCID 7021151Dimethyl((3S)-4-phenyl-3-(Boc-amino)-2-oxobutyl)phosphonateHCID 66938886{1-[4-(4-Nitro-phenyl)-6-oxo-1,6-dihydro-pyridin-2-yl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester

Product 1

HCID 66938310[(E)-(S)-1-benzyl-4-(4-nitro-phenyl)-2-oxo-but-3-enyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

{1-[4-(4-Nitro-phenyl)-6-oxo-1,6-dihydro-pyridin-2-yl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester: A suspension of ((S)-3-tert-butoxycarbonylamino-2-oxo-4-phenyl-butyl)-phosphonic acid dimethyl ester (1.114 g, 3 mmol, Resmini, M. et al., Tetrahedron Asymmetry, 2004, 15, 1847), 4-nitrobenzaldehyde (0.453 g, 3 mmol) and potassium carbonate (0.415 g, 3 mmol) in ethanol (60 mL) was stirred at rt for 5 h. The reaction mixture was diluted with EtOAc, washed with water, brine, and dried over Na2SO4, filtered and concentrated to give 1.276 g of [(E)-(S)-1-benzyl-4-(4-nitro-phenyl)-2-oxo-but-3-enyl]-carbamic acid tert-butyl ester as a yellow solid. This yellow solid was suspended in ethanol (30 mL), then 1-ethoxycarbonylmethyl-pyridinium chloride (0.605 g, 3 mmol) and ammonium acetate (4.63 g, 60 mmol) were added. The reaction mixture was stirred at rt for 10 min, then heated at 80° C. for 5 h to yield a white suspension. The reaction was cooled to rt and the solid was collected by filtration, washed with methanol, and dried in vacuo (50° C.) to give 0.85 g (62%) of 64A as a white solid. LCMS m/z 436.3 (M+H)+. 1HNMR (400 MHz, DMSO-D6) δ: 1.26 (s, 9 H), 2.76-2.82 (m, 1 H), 3.01-3.06 (m, 1 H), 4.68-4.74 (m, 1 H), 6.54-6.60 (m, 2 H), 7.18-7.29 (m, 5 H), 7.40 (d, J=9.2 Hz, 1 H), 7.91 (d, J=8.8 Hz, 2 H), 8.34 (d, J=8.8 Hz, 2 H), 11.96 (s, 1 H).

Workup

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-6b6e615cdacf4e10ab60d51a845e2736
Source dataset
uspto-grants-2012_08
Patent number
US08252830B2

Reaction notes

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