(S)-Tert-butyl 2,2-dimethyl-4-(2-oxoethyl)oxazolidine-3-carboxylate → (S)-4-((S)-2-hydroxy-propyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester

HRID 19036Notes

Reaction equation

HRID 19036 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH:14]=[O:15])[CH2:11][O:10][C:9]1([CH3:17])[CH3:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][Mg]Br>O1CCCC1.C(OCC)C>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][C@@H:14]([OH:15])[CH3:18])[CH2:11][O:10][C:9]1([CH3:17])[CH3:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 10586317(S)-Tert-butyl 2,2-dimethyl-4-(2-oxoethyl)oxazolidine-3-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 59173108(S)-4-((S)-2-hydroxy-propyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled solution of (S)-2,2-dimethyl-4-(2-oxo-ethyl)-oxazolidine-3-carboxylic acid t-butyl ester (2.05 g, 8.43 mmol) in dry tetrahydrofuran (25 mL) was added 1.4M methyl magnesium bromide in diethyl ether (6.02 mL) at −78° C. The mixture was stirred at −78° C. for 30 min and then warmed to −5° C. The mixture was extracted with diethyl ether and ammonium chloride solution. The organic layer was dried and concentrated. The crude mixture was purified by ISCO flash chromatography (0 to 60% ethyl acetate/hexanes) to give two fractions. The first fraction afforded (S)-4-((S)-2-hydroxy-propyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester as a colorless oil (870 mg): 1H NMR (300 MHz, CDCl3) δ ppm 1.20 (d, J=6.0 Hz, 3H), 1.42-1.60 (m, 1H), 1.50 (s, 12H), 1.55 (s, 3H), 1.68-1.88 (m, 1H), 3.66 (d, J=8.8 Hz, 1H), 3.69-3.80 (m, 1H), 3.94-4.08 (m, 1H), 4.17-4.30 (m, 1H), 4.62 (br. s., 1H); The second fraction afforded (S)-4-((R)-2-hydroxy-propyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester as a white solid (740 mg): 1H NMR (300 MHz, CDCl3) δ ppm 1.22 (d, J=6.0 Hz, 3H), 1.49 (s, 12H), 1.58 (br. s., 3H), 1.75-1.90 (m, 2H), 2.56 (br. s., 1H), 3.75-3.93 (m, 2H), 3.95-4.05 (m, 1H), 4.03-4.20 (m, 1H).

Workup

  1. temperaturewarmed to −5° C
  2. extractionThe mixture was extracted with diethyl ether and ammonium chloride solution
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customThe crude mixture was purified by ISCO flash chromatography (0 to 60% ethyl acetate/hexanes)
  6. customto give two fractions

Sources & evidence

ORD record
ord-c998ee0b7cbd49e2aca538f3ae03d3e0
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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