HCID 68283302, compound → HCID 68283131, compound

HRID 1527317Notes

Reaction equation

HRID 1527317 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[CH2:13])[CH2:10][C@H:9]1[C:14](=[O:27])[NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:26])([F:25])[F:24])[CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CCOC(C)=O.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH3:13])[CH2:10][C@H:9]1[C:14](=[O:27])[NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:24])([F:25])[F:26])[CH:17]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 1

HCID 68283302HCID 68283302, compound

Product 1

HCID 68283131HCID 68283131, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-2-(3-trifluoromethoxy-phenylcarbamoyl)-4-methylene-pyrrolidine-1-carboxylic acid tert-butyl ester (0.5 g, 1.29 mmol) in EtOAc (15 mL) was added Pd/C (10%) and the reaction mixture was placed under hydrogen atmosphere overnight. The reaction mixture was filtered on a pad of Celite, the catalyst residue was washed with EtOAc and the solvent was concentrated. The crude material was purified by preparative HPLC (waters SunFire C18-ODB, 5 μm, 30×100 mm, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min, loading 150 mg per run) to give after lyophilization of the purified fractions the desired compounds: (2S,4S)-2-(3-trifluoromethoxy-phenylcarbamoyl)-4-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester: tR (HPLC conditions b): 5.34 min; LC/MS: 387.0 [M−H]−; (2S,4R)-2-(3-trifluoromethoxy-phenylcarbamoyl)-4-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester: tR (HPLC conditions b): 5.53 min; MS (LC/MS): 387.0 [M−H]−.

Workup

  1. filtrationThe reaction mixture was filtered on a pad of Celite
  2. washthe catalyst residue was washed with EtOAc
  3. concentrationthe solvent was concentrated
  4. customThe crude material was purified by preparative HPLC (waters SunFire C18-ODB, 5 μm, 30×100 mm, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min, loading 150 mg per run)
  5. customto give after lyophilization of the
  6. custompurified fractions the desired compounds
  7. custom5.34 min
  8. custom5.53 min

Sources & evidence

ORD record
ord-341de8d7d3fa4d7ab9679e2bb502cb0a
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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