Water → HCID 59756825, compound

HRID 1665805Notes

Reaction equation

HRID 1665805 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([Cl:23])[CH:21]=2)[C:16]([C:24](=[O:29])C(F)(F)F)=[CH:15]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[OH2:32]>CN(C)C=O.COC(C)(C)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([Cl:23])[CH:21]=2)[C:16]([C:24]([OH:32])=[O:29])=[CH:15]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 962WaterHCID 24758Sodium hydrideHCID 59756823HCID 59756823, compound

Product 1

HCID 59756825HCID 59756825, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of 1.7 g (4.0 mmol) (S)-2-[6-chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-ylmethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester and 1.0 g (22 mmol) sodium hydride (50% in oil) in 40 ml dry N,N-dimethylformamide were added dropwise 0.36 ml (20 mmol) water under water-bath cooling. After stirring for 45 min the reaction mixture was diluted with 80 ml tert-butyl methyl ether. The organic layer was extracted with aqueous 1 M sodium hydroxide solution (2×100 ml). The combined aqueous layers were acidified to pH 2 with ice-cold aqueous hydrochloric acid solution and extracted with ethyl acetate (3×100 ml). The combined ethyl acetate layers were dried over sodium sulfate and concentrated to dryness to give the title compound (1.4 g, 96%) as a light yellow solid.

Workup

  1. temperaturecooling
  2. extractionThe organic layer was extracted with aqueous 1 M sodium hydroxide solution (2×100 ml)
  3. extractionextracted with ethyl acetate (3×100 ml)
  4. dry with materialThe combined ethyl acetate layers were dried over sodium sulfate
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-5239ad29aaec4dcf92e9195c0af8094e
Source dataset
uspto-grants-2011_10
Patent number
US08039624B2

Reaction notes

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