Water → 4-(3,4-Difluorophenyl)-5-methyl-oxazolidin-2-one

HRID 1832161Notes

Reaction equation

HRID 1832161 reaction equation
C([O:5][C:6](=[O:20])[NH:7][CH:8]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=1)[CH:9](O)[CH3:10])(C)(C)C.[H-].[Na+].O>C1COCC1>[F:19][C:14]1[CH:13]=[C:12]([CH:8]2[CH:9]([CH3:10])[O:20][C:6](=[O:5])[NH:7]2)[CH:17]=[CH:16][C:15]=1[F:18]

Participants

5

Reactant 3

HCID 962WaterHCID 24758Sodium hydride2×HCID 22048785[1-(3,4-Difluorophenyl)-2hydroxy-propyl]-carbamic acid-tert-butyl ester

Product 1

HCID 220486254-(3,4-Difluorophenyl)-5-methyl-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

Into a well-stirred solution of [1-(3,4-difluorophenyl)-2-hydroxy-propyl]-carbamic acid-tert-butyl ester (0.43 g, 1.5 mmol) in THF (20 mL) was added 95% NaH (0.09 g, 3.8 mmol) at room temperature. When the reaction was carried out on a larger (>5 g) scale, 1.0 equivalent of KH and 1.5 eq. of NaH was used as the base. The resulting suspension was stirred for 3 h at about 35° C. (warm water bath) and then quenched carefully with ice. The biphasic mixture was extracted with 100 mL of EtOAc, washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo. The two diastereomers were separated by column chromatography over silica gel (First isomer: 0.16 g, Rf=0.6, 3:1 hexane-EtOAc; second isomer: 0.18 g, Rf=0.5, 3:1 hexane-EtOAc). NOE experiments suggested that the first diastereomer had the methyl and the aryl group in trans configuration while the second diastereomer had cis relationship between the two groups. The 1H NMR spectrum for the trans diastereomer is as follows. 1H NMR (CDCl3) δ 1.49 (d, J=6.0 Hz, 3H), 4.37 (dq, J=6.0 Hz, J=7.2 Hz, 1H), 4.45 (d, J=7.2 Hz, 1H), 6.63 (br s, 1H), 7.08–7.28 (m, 3H).

Workup

  1. customquenched carefully with ice
  2. extractionThe biphasic mixture was extracted with 100 mL of EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customThe two diastereomers were separated by column chromatography over silica gel (First isomer: 0.16 g, Rf=0.6, 3:1 hexane-EtOAc; second isomer: 0.18 g, Rf=0.5, 3:1 hexane-EtOAc)

Sources & evidence

ORD record
ord-2d54136a894c4f19a32f95e47b04e68a
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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