Phosphorus oxychloride → tert-butyl(2S,3S)-7-bromo-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

HRID 1486075Notes

Reaction equation

HRID 1486075 reaction equation
[Br:1][C:2]1[CH:22]=[CH:21][C:5]2[NH:6][C@@H:7]([CH3:20])[C@H:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:9](=[O:11])[NH:10][C:4]=2[CH:3]=1.[CH3:23][S:24]([CH2:27][C:28](O)=[O:29])(=[O:26])=[O:25].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[Br:1][C:2]1[CH:22]=[CH:21][C:5]2[N:6]([C:28](=[O:29])[CH2:27][S:24]([CH3:23])(=[O:26])=[O:25])[C@@H:7]([CH3:20])[C@H:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:9](=[O:11])[NH:10][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 37328412-Methanesulfonylacetic acidHCID 131736773tert-butyl(2S,3S)-7-bromo-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

Product 1

HCID 131736774tert-butyl(2S,3S)-7-bromo-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamateYield 94%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of tert-butyl(2S,3S)-7-bromo-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (130 mg, 351 μmol) and 2-(methylsulfonyl)acetic acid (53.4 mg, 386 μmol) in pyridine (3.51 ml) was added phosphoryl chloride (64.3 μl, 702 μmol). The reaction was stirred at 0° C. for 30 min, then quenched by the addition of H2O and extracted with EtOAc. The combined organic layers were washed with 1 N aq. citric acid, H2O, sat. aq. NaHCO3, and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(2S,3S)-7-bromo-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (161 mg, 94%) as a white solid. MS m/z 512/514 (MNa)+.

Workup

  1. customquenched by the addition of H2O
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with 1 N aq. citric acid, H2O, sat. aq. NaHCO3, and sat. aq. NaCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-b0fac0f3c6064546a56dc534994faf6c
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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