Benzyl Alcohol → HCID 68561558, compound

HRID 20466Notes

Reaction equation

HRID 20466 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]([O:15][C:16]([N:18]1[C@@H:22]([C@H:23]([O:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C@@H:24]([N:34]([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:25][C:26]2[CH:31]=[C:30](F)[CH:29]=[C:28]([F:33])[CH:27]=2)[CH2:21][O:20][C:19]1([CH3:58])[CH3:57])=[O:17])([CH3:14])([CH3:13])[CH3:12].[Cl-].[NH4+]>CN1CCCC1=O.C(OCC)(=O)C>[C:11]([O:15][C:16]([N:18]1[C@@H:22]([C@H:23]([O:49][CH2:50][C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[C@@H:24]([N:34]([CH2:42][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH2:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH2:25][C:26]2[CH:27]=[C:28]([F:33])[CH:29]=[C:30]([O:10][CH2:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=3)[CH:31]=2)[CH2:21][O:20][C:19]1([CH3:58])[CH3:57])=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 68558730HCID 68558730, compound

Product 1

HCID 68561558HCID 68561558, compoundYield 94.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Add NaH (12.5 g, 60% mineral oil suspension, 312.5 mmol) in portions to a solution of benzyl alcohol (32 mL, 309.2 mmol) in N-methylpyrrolidinone (1 L). Stir the reaction mixture at r.t. until no gas evolution is detected. Add (R)-4-[(1R,2S)-3-(3,5-difluorophenyl)-1-benzyloxy-2-dibenzylaminopropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (130 g) to the mixture and warm it up to 90° C. After 45 min, allow to cool to room temperature and add saturated aqueous ammonium chloride. Dilute with ethyl acetate (2 L) and wash with saturated aqueous sodium chloride (2×1.5 L). Dry the organic layer on MgSO4, filter and concentrate. Subject residue to silical gel chromatography, eluting with 2-4% ethyl acetate in hexanes, to provide 139.45 g (94%) of the desired compound as a white solid.

Workup

  1. temperatureto cool to room temperature
  2. washwash with saturated aqueous sodium chloride (2×1.5 L)
  3. customDry the organic layer on MgSO4
  4. filtrationfilter
  5. concentrationconcentrate
  6. washSubject residue to silical gel chromatography, eluting with 2-4% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-7e7a933727d947e28778f66b274fdb21
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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