Sodium borohydride → (2R,5R)-5-[(1S,2S)-2-Amino-3-(3-chloro-5-fluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester

HRID 20362

Reaction equation

HRID 20362 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:28])[C@@H:15]([N+:25]([O-])=O)[CH2:16][C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([Cl:24])[CH:18]=2)[CH2:12][O:11][C@@H:10]([O:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO.[Ni](Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:28])[C@@H:15]([NH2:25])[CH2:16][C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([Cl:24])[CH:18]=2)[CH2:12][O:11][C@@H:10]([O:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 68562233(2R,5R)-5-[(1R,2S)-3-(3-Chloro-5-fluorophenyl)-1-hydroxy-2-nitropropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68561142(2R,5R)-5-[(1S,2S)-2-Amino-3-(3-chloro-5-fluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl esterYield 100%

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent

Procedure

Dissolve (2R,5R)-5-[(1R,2S)-3-(3-chloro-5-fluorophenyl)-1-hydroxy-2-nitropropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester (0.455 g, 0.901 mmol) in methanol (8 mL) and stir at room temperature in an oil bath. Add anhydrous nickel (II) chloride (0.175 g, 1.35 mmol) followed by sodium borohydride (0.170 mg, 4.50 mmol) in 3 portions over 5 minutes and stir for 15 minutes. Add water (2 mL), 0.1 N sodium hydroxide (2 mL) and extract with ethyl acetate (2×30 mL). Combine organic extracts, wash with saturated aqueous sodium chloride (30 mL), dry (sodium sulfate), filter through a pad of Celite® and concentrate to give the desired compound as a colorless oil (0.428 g).

Workup

  1. stirringstir for 15 minutes
  2. extractionAdd water (2 mL), 0.1 N sodium hydroxide (2 mL) and extract with ethyl acetate (2×30 mL)
  3. washCombine organic extracts, wash with saturated aqueous sodium chloride (30 mL)
  4. dry with materialdry (sodium sulfate)
  5. filtrationfilter through a pad of Celite®
  6. concentrationconcentrate

Sources & evidence

ORD record
ord-8f93c0006e9041f8b7a31052bf892019
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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