Acetaldehyde → (S)-4-[(benzyl-ethyl-amino)-methyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1911568Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:24](=O)[CH3:25].[BH3-]C#N.[Na+]>CO.[Cl-].[Cl-].[Zn+2]>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][N:14]([CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:24][CH3:25])[CH2:11][O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of (S)-4-(benzylamino-methyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (800 mg) at r.t. in methanol (10 ml) under an argon atmosphere were added acetaldehyde (0.70 ml), ZnCl2 (1.36 g) and NaBH3CN (0.47 g). The mixture was warmed to 50° C. and stirring at that temperature was continued for 17 h. The mixture was cooled to r.t. and partitioned between ammonium chloride solution and dichloromethane. The combined organic layers were dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography (column: Isolute® Flash-NH2 from Separtis; eluent: heptane/ethyl acetate=1:1) to give (S)-4-[(benzyl-ethyl-amino)-methyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (160 mg, 18%) as colorless oil. MS (ISP): 293.5 ([M-tBu+H]+)

Workup

temperatureThe mixture was cooled to r.t.
custompartitioned between ammonium chloride solution and dichloromethane
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by column chromatography (column: Isolute® Flash-NH2 from Separtis; eluent: heptane/ethyl acetate=1:1)

Sources & evidence

ORD record: ord-ae753c0259174bb1bd218457ee978110
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08604061B2

Reaction notes

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