Water → HCID 68561211, compound

HRID 20457Notes

Reaction equation

HRID 20457 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[C@@H:15]([C@@H:16]([O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C@@H:17]([N:27]([CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:18][C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[C:21](F)[CH:20]=2)[CH2:14][O:13][C@@H:12]([O:50][CH2:51][C:52]([CH3:56])([CH3:55])[CH2:53][F:54])[C@@H:11]1[CH3:57])=[O:9])([CH3:6])([CH3:5])[CH3:4].O.CN1C[CH2:63][CH2:62][C:61]1=[O:65]>C(O)CC>[C:3]([O:7][C:8]([N:10]1[C@@H:15]([C@@H:16]([O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C@@H:17]([N:27]([CH2:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:18][C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([O:65][CH2:61][CH2:62][CH3:63])[CH:20]=2)[CH2:14][O:13][C@@H:12]([O:50][CH2:51][C:52]([CH3:56])([CH3:55])[CH2:53][F:54])[C@@H:11]1[CH3:57])=[O:9])([CH3:4])([CH3:6])[CH3:5]

Participants

6

Reactant 4

HCID 962WaterHCID 13387N-methyl-2-pyrrolidone2×HCID 24758Sodium hydrideHCID 68558843HCID 68558843, compound

Product 1

HCID 68561211HCID 68561211, compound

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Procedure

Stir a mixture of sodium hydride (115 mg, 2.89 mmol, 60% in mineral oil) in N-methyl-2-pyrrolidinone (960 μL) and 1-propanol (234 μL) for 10 minutes and then add a solution of (2R,3S,5R)-5-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-2-(3-fluoro-2,2-dimethylpropoxy)-3-methylmorpholine-4-carboxylic acid tert-butyl ester (440 mg, 0.57 mmol) in N-methyl-2-pyrrolidinone (1 mL) and stir in a sealed vial at 90° C. for 4 hours. Cool to room temperature and pour reaction mixture into water and extract well with ethyl acetate. Wash the organic phase with water followed by saturated aqueous sodium chloride and concentrate under reduced pressure. Subject the resulting residue to silica gel chromatography, eluting with hexane containing from 0-50% ethyl acetate to provide the desired compound.

Workup

  1. stirringstir in a sealed vial at 90° C. for 4 hours
  2. additionpour
  3. extractionextract well with ethyl acetate
  4. washWash the organic phase with water
  5. concentrationconcentrate under reduced pressure
  6. washeluting with hexane containing from 0-50% ethyl acetate

Sources & evidence

ORD record
ord-9bc7e15ab0134faf8c537fe7fd11d191
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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