2-Methoxypropane → (2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-benzyloxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 732379Notes

Reaction equation

HRID 732379 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@@H:9]1[C@@H:21]([OH:36])[C@@H:22]([NH:32][C:33](=[O:35])[CH3:34])[CH2:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:37][C:38]1C=CC(S([O-])(=O)=O)=C[CH:39]=1.C1C=C[NH+]=CC=1.COC(C)C>ClCCl.CC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:10][C@@H:9]1[C@H:21]1[O:36][C:38]([CH3:39])([CH3:37])[N:32]([C:33](=[O:35])[CH3:34])[C@H:22]1[CH2:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 117212-MethoxypropaneHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 68817282(2R,4R)-2-[(1S,2S)-2-Acetylamino-3-(3,5-difluoro-phenyl)-1-hydroxy-propyl]-4-benzyloxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68814284(2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-benzyloxy-pyrrolidine-1-carboxylic acid tert-butyl esterYield 734.4%

Reagents, catalysts & solvents 1

HCID 21584124Propan-2-one--dichloromethane (1/1)Solvent

Procedure

Dissolve (2R,4R)-2-[(1S,2S)-2-Acetylamino-3-(3,5-difluoro-phenyl)-1-hydroxy-propyl]-4-benzyloxy-pyrrolidine-1-carboxylic acid tert-butyl ester (0.150 g, 0.3 mmol) in 1:1 dichloromethane/acetone (5 mL). Add PPTS (pyridine/p-toluene sulfonic acid) (0.03 mmol) and 2-methoxypropane (1.5 mmol). When the reaction is complete by TLC (15 minutes), concentrate the reaction mixture under reduced pressure. Dissolve the residue in ethyl acetate and wash with saturated aqueous sodium bicarbonate followed by saturated aqueous sodium chloride. Dry over magnesium sulfate, concentrate under reduced pressure, and subject the residue to silica gel chromatography, eluting with ethyl acetate/hexane to provide the desired compound (0.120 g, 75%).

Workup

  1. customis complete by TLC (15 minutes)
  2. concentrationconcentrate the reaction mixture under reduced pressure
  3. dissolutionDissolve the residue in ethyl acetate
  4. washwash with saturated aqueous sodium bicarbonate
  5. dry with materialDry over magnesium sulfate
  6. concentrationconcentrate under reduced pressure
  7. washeluting with ethyl acetate/hexane

Sources & evidence

ORD record
ord-f840b3c87d344e82962d2d74ddff01fe
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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