3-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde, (R)-(+)- → 4-(R)-[3-(3-Acetoxyphenyl)-1-(R)-hydroxy-2-(S)-nitropropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

HRID 20347Notes

Reaction equation

HRID 20347 reaction equation
[N+:1]([CH2:4][CH2:5][C:6]1[CH:7]=[C:8]([O:12][C:13](=[O:15])[CH3:14])[CH:9]=[CH:10][CH:11]=1)([O-:3])=[O:2].[CH:16]([C@H:18]1[CH2:22][O:21][C:20]([CH3:24])([CH3:23])[N:19]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[O:17].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[C:28]([O:27][C:25]([N:19]1[C@@H:18]([C@@H:16]([OH:17])[C@@H:4]([N+:1]([O-:3])=[O:2])[CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13](=[O:15])[CH3:14])[CH:7]=2)[CH2:22][O:21][C:20]1([CH3:24])[CH3:23])=[O:26])([CH3:31])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 1787923-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde, (R)-(+)-HCID 2724141Tetrabutylammonium FluorideHCID 68563888Acetic acid 3-(2-nitroethyl)-phenyl ester

Product 1

HCID 685609864-(R)-[3-(3-Acetoxyphenyl)-1-(R)-hydroxy-2-(S)-nitropropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl esterYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Dissolve acetic acid 3-(2-nitroethyl)-phenyl ester (25.53 g, 121.6 mmol) and tert-butyl (R)-(+)-4-formyl-2,2-dimethyl-3-oxazolidinecarboxylate (Gardner's aldehyde) (22.38 g, 97.61 mmol) in dry tetrahydrofuran (200 mL). Cool in ice bath and add tetrabutylammonium fluoride (98 mL, 98 mmol, 1.0 M in tetrahydrofuran) and stir for 15 minutes. Pour into ice water (2.7 L), wash with 1 N hydrochloric acid (200 mL), saturated aqueous sodium chloride, dry (magnesium sulfate), filter through a pad of silica gel and concentrate. Purify using silica gel chromatography, eluting with 5:95 ethyl acetate:dichloromethane, followed by 2 separate crystallizations using hexanes/dichloromethane to give the desired compound (18.372 g, 43% total yield).

Workup

  1. temperatureCool in ice bath
  2. washwash with 1 N hydrochloric acid (200 mL), saturated aqueous sodium chloride
  3. dry with materialdry (magnesium sulfate)
  4. filtrationfilter through a pad of silica gel
  5. concentrationconcentrate
  6. customPurify
  7. washeluting with 5:95 ethyl acetate
  8. customseparate
  9. customcrystallizations

Sources & evidence

ORD record
ord-2f7897f64e5247c789115d364de75882
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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