Ammonium Chloride → (1S,5R)-5-Fluoro-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester

HRID 1917338Notes

Reaction equation

HRID 1917338 reaction equation
[C:1]([O:5][C:6]([C@@:8]1([CH2:23][CH2:24]COS(C2C=CC=CC=2)(=O)=O)[CH:12]([F:13])[C:11](=[O:14])[N:10]([C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:36][Si](C)(C)[N-][Si](C)(C)C.[K+].[Cl-].[NH4+]>O1CCCC1>[C:1]([O:5][C:6]([C@@:8]12[CH2:23][CH2:24][CH2:36][C@:12]1([F:13])[C:11](=[O:14])[N:10]([C@@H:15]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH3:16])[CH2:9]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 86664648(3S)-3-(3-benzenesulfonyloxy-1-propyl)-4-Fluoro-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 67490944(1S,5R)-5-Fluoro-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(3S)-3-(3-benzenesulfonyloxy-1-propyl)-4-Fluoro-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (10.9 g) was dissolved in tetrahydrofuran (350 mL), and the atmosphere was replaced with argon. Then, potassium hexamethyldisilazide (0.5 M solution in toluene) (86.5 mL) was added dropwise at −15° C., and the mixture was stirred at 0° C. for 1.5 hours. After cooling to −10° C., saturated aqueous ammonium chloride (100 mL) was added dropwise, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was extracted with a 10% citric acid solution and ethyl acetate. Then, the organic layer was washed with brine, dried over anhydrous sodium sulfate, and filtered. Thereafter, the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane:ethyl acetate=9:1→7:1) to give 4.36 g of the title compound as a pale yellow solid.

Workup

  1. temperatureAfter cooling to −10° C.
  2. stirringthe mixture was stirred at room temperature for 30 minutes
  3. extractionThe reaction solution was extracted with a 10% citric acid solution and ethyl acetate
  4. washThen, the organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customThereafter, the solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-619d2c53a0d54559b45140b212c39ec6
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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