Water → (R)-5-[(1S,2S)-2-Amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2-ethoxymorpholine-4-carboxylic acid tert-butyl ester

HRID 20392

Reaction equation

HRID 20392 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH: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]([F:24])[CH:18]=2)[CH2:12][O:11][C@@H:10]([O:29][CH2:30][CH3:31])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].O>CO.[Ni](Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH:13]([C@@H:14]([OH:28])[C@@H:15]([NH2:25])[CH2:16][C:17]2[CH:18]=[C:19]([F:24])[CH:20]=[C:21]([F:23])[CH:22]=2)[CH2:12][O:11][C@@H:10]([O:29][CH2:30][CH3:31])[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydrideHCID 68564103(R)-5-[(1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-2-nitropropyl]-2-ethoxymorpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68563667(R)-5-[(1S,2S)-2-Amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2-ethoxymorpholine-4-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent

Procedure

To a solution of (R)-5-[(1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-2-nitropropyl]-2-ethoxymorpholine-4-carboxylic acid tert-butyl ester (0.145 g, 0.325 mmol) in methanol (5 mL) at room temperature add nickel (II) chloride (0.063 g, 0.487 mmol) and then sodium borohydride (0.061 g, 1.62 mmol) portionwise. Stir 30 minutes, add water (˜3 mL) and concentrate. Dilute with ethyl acetate and filter through Celite®. Partition the filtrate between ethyl acetate and water. Dry the ethyl acetate layer (magnesium sulfate), filter and concentrate to give the desired compound as a white solid.

Workup

  1. concentrationconcentrate
  2. additionDilute with ethyl acetate
  3. filtrationfilter through Celite®
  4. customPartition the filtrate between ethyl acetate and water
  5. dry with materialDry the ethyl acetate layer (magnesium sulfate)
  6. filtrationfilter
  7. concentrationconcentrate

Sources & evidence

ORD record
ord-c6d13efcbadb45c496155abf183d442b
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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