Acetyl chloride → HCID 76021591, compound

HRID 2065404Notes

Reaction equation

HRID 2065404 reaction equation
F[C:2](F)(F)[C:3](O)=[O:4].[NH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]([N:17]2[CH2:21][CH:20]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:19]3([C:34]4[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=4)[NH:28][C:27]3=[O:36])[CH:18]2[C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[C:38]=2[F:44])=[O:16])[CH2:10][CH2:9]1.C(N(CC)CC)C.C(Cl)(=O)C>O1CCCC1>[C:3]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]([N:17]2[CH2:21][CH:20]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:19]3([C:34]4[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=4)[NH:28][C:27]3=[O:36])[CH:18]2[C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[C:38]=2[F:44])=[O:16])[CH2:10][CH2:9]1)(=[O:4])[CH3:2]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 76021589HCID 76021589, compound

Product 1

HCID 76021591HCID 76021591, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carboxylic acid piperidin-4-ylamide trifluoroacetic acid (80 mg, 0.12 mmol) in tetrahydrofuran (2 mL) at 0° C. was added triethylamine (0.042 mL, 0.3 mmol) and acetyl chloride (10.4 mg, 0.13 mmol). The mixture was stirred at room temperature for 0.5 h. The mixture was concentrated, and the residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated. The residue was recrystallized in dichloromethane and hexanes to give as rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carboxylic acid (1-acetyl-piperidin-4-yl)-amide as a white solid (65 mg, 92%)

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was recrystallized in dichloromethane

Sources & evidence

ORD record
ord-4ae484fa845442eba008c7d6b564997f
Source dataset
uspto-grants-2012_10
Patent number
US08288431B2

Reaction notes

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