Water → HCID 67280318, compound

HRID 1516328Notes

Reaction equation

HRID 1516328 reaction equation
[F:1][C:2]1[CH:34]=[CH:33][C:5]([C:6]([NH:8][C@H:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([N:18]4[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][C:19]4=O)[CH:16]=3)[CH2:11][C@@H:10]2[OH:32])=[O:7])=[CH:4][CH:3]=1.O.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([NH:8][C@H:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([N:18]4[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:28])[CH3:29])=[O:25])[CH2:20][CH2:19]4)[CH:16]=3)[CH2:11][C@@H:10]2[OH:32])=[O:7])=[CH:33][CH:34]=1

Participants

6

Reactant 3

HCID 962WaterHCID 516892Sodium BicarbonateHCID 67281262HCID 67281262, compound

Product 1

HCID 67280318HCID 67280318, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cool a solution of tert-butyl 4-[(2S,3S)-3-[(4-fluorobenzoyl)amino]-2-hydroxy-indan-5-yl]-3-oxo-piperazine-1-carboxylate (8.85 g, 18.9 mmol) in anhydrous tetrahydrofuran (40 mL) in an ice bath for 30 min. and add borane-dimethyl sulfide complex (2 M, 37.7 mL, 75.40 mmol) under nitrogen. Warm the mixture to room temperature and stir for 1.5 hr. Add a second portion of borane-dimethyl sulfide complex (2 M, 9.42 mL, 18.9 mmol) at room temperature and stir for one hour. Cool in an ice bath for 10 min and carefully add water dropwise, followed by addition of saturated sodium bicarbonate solution (50 mL). Dilute the resulting suspension with ethyl acetate (150 mL). Wash the organic portion with brine, dry over sodium sulfate, and concentrate in vacuo. Purify the crude product by flash chromatography (120 g silica, 40 to 50% ethyl acetate/hexanes) to obtain the title compound (6.8 g, 79%). LC-ES/MS m/z 456 [M+H]+.

Workup

  1. additionadd borane-dimethyl sulfide complex (2 M, 37.7 mL, 75.40 mmol) under nitrogen
  2. additionAdd a second portion of borane-dimethyl sulfide complex (2 M, 9.42 mL, 18.9 mmol) at room temperature
  3. stirringstir for one hour
  4. temperatureCool in an ice bath for 10 min
  5. washWash the organic portion with brine
  6. dry with materialdry over sodium sulfate
  7. concentrationconcentrate in vacuo
  8. customPurify the crude product by flash chromatography (120 g silica, 40 to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0d22b34e54b94aec91f6b7e4d359a945
Source dataset
uspto-grants-2012_07
Patent number
US08227468B2

Reaction notes

Loading…