4-Acetylbenzoic Acid → [(2S,3S)-1-(4-acetyl-benzoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-carbamic acid tert-butyl ester

HRID 1486034Notes

Reaction equation

HRID 1486034 reaction equation
P(Cl)(Cl)(Cl)=O.[C:6]([O:10][C:11](=[O:26])[NH:12][C@H:13]1[C@H:19]([CH3:20])[NH:18][C:17]2[CH:21]=[CH:22][CH:23]=[CH:24][C:16]=2[NH:15][C:14]1=[O:25])([CH3:9])([CH3:8])[CH3:7].[C:27]([C:30]1[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][CH:31]=1)(=[O:29])[CH3:28]>N1C=CC=CC=1.O>[C:6]([O:10][C:11](=[O:26])[NH:12][C@H:13]1[C@H:19]([CH3:20])[N:18]([C:34](=[O:35])[C:33]2[CH:32]=[CH:31][C:30]([C:27](=[O:29])[CH3:28])=[CH:38][CH:37]=2)[C:17]2[CH:21]=[CH:22][CH:23]=[CH:24][C:16]=2[NH:15][C:14]1=[O:25])([CH3:7])([CH3:8])[CH3:9]

Participants

6

Reactant 3

HCID 114704-Acetylbenzoic AcidHCID 24813Phosphorus oxychlorideHCID 90082343tert-butyl(2S,3S)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

Product 1

HCID 90082505[(2S,3S)-1-(4-acetyl-benzoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-carbamic acid tert-butyl esterYield 66.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

Phosphoryl chloride (0.16 ml, 1.72 mmol) was added to a solution of ((2S,3S)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-carbamic acid tert-butyl ester (0.5 g, 1.72 mmol) and 4-acetyl-benzoic acid (0.25 g, 1.54 mmol) in pyridine (15 ml) at 0° C., stirring continued for 2 h. The reaction mixture was diluted with water (50 ml) and extracted with ethyl acetate (2×60 mL). The organic layers were combined, washed with 10% aqueous citric acid (1×15 mL), water (1×15 mL) and a saturated aqueous solution of sodium hydrogen carbonate (1×15 mL) and brine. The organic extract was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted with 10 to 60% v/v ethyl acetate hexanes to give [(2S,3S)-1-(4-acetyl-benzoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-carbamic acid tert-butyl ester (0.45 g, 60%).

Workup

  1. extractionextracted with ethyl acetate (2×60 mL)
  2. washwashed with 10% aqueous citric acid (1×15 mL), water (1×15 mL)
  3. extractionThe organic extract
  4. dry with materialwas dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by chromatography over silica gel gradient
  8. washeluted with 10 to 60% v/v ethyl acetate hexanes

Sources & evidence

ORD record
ord-87e5852b7d3d41c9aea67930d328d964
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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