tert-Butyl bromoacetate → (3S)-3-(4-Chlorobenzyl)-4-((4R,5S)-4-methyl-2-oxo-5-phenyl-oxazolidin-3-yl)-4-oxo-butyric acid tert-butyl ester

HRID 1192345Notes

Reaction equation

HRID 1192345 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][C:20]([N:22]2[C@H:26]([CH3:27])[C@H:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[O:24][C:23]2=[O:34])=[O:21])=[CH:14][CH:13]=1.[C:35]([O:39][C:40](=[O:43])[CH2:41]Br)([CH3:38])([CH3:37])[CH3:36]>C1COCC1>[C:35]([O:39][C:40](=[O:43])[CH2:41][C@H:19]([CH2:18][C:15]1[CH:14]=[CH:13][C:12]([Cl:11])=[CH:17][CH:16]=1)[C:20]([N:22]1[C@H:26]([CH3:27])[C@H:25]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[O:24][C:23]1=[O:34])=[O:21])([CH3:38])([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 15162208(4R,5S)-3-[3-(4-Chlorophenyl)-propionyl]-4-methyl-5-phenyl-oxazolidin-2-one

Product 1

HCID 67540437(3S)-3-(4-Chlorobenzyl)-4-((4R,5S)-4-methyl-2-oxo-5-phenyl-oxazolidin-3-yl)-4-oxo-butyric acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

NaHMDS (1.0M, 17 mL, 17 mmol) was added to a stirred solution of (4R,5S)-3-[3-(4-Chlorophenyl)-propionyl]-4-methyl-5-phenyl-oxazolidin-2-one (4.8 g, 14 mmol) in THF (200 mL) at −78° C. under N2. Stirred at −78° C. for 45 minutes and then Bromo-acetic acid tert-butyl ester (2.5 mL, 17 mmol) was added dropwise over 10 minutes. The solution was allowed to warm to −20° C. over 4 hours and then quenched with saturated aqueous NH4Cl. The product was extracted into EtOAc (2×300 mL), dried over Na2SO4, concentrated in vacuo and purified by column chromatography on silica (20% EtOAc/hexanes) to give (3S)-3-(4-Chlorobenzyl)-4-((4R,5S)-4-methyl-2-oxo-5-phenyl-oxazolidin-3-yl)-4-oxo-butyric acid tert-butyl ester (5.1 g, 80%.) 1H NMR (CDCl3, 400 MHz) δ 7.44-7.21 (9H, m), 5.45 (1H, d, J 7.3 Hz), 4.68-4.62 (1H, m), 4.51-4.42 (1H, m), 3.01 (1H, dd, J 13.0 and 6.2 Hz), 2.78 (1H, dd, J 16.7 and 10.6 Hz), 2.63 (1H, dd, J 13.2 and 9.0 Hz), 2.32 (1H, dd, J 6.7 and 4.3 Hz), 1.38 (9H, s), 0.89 (3H, d, J 6.6 Hz.)

Workup

  1. temperatureto warm to −20° C. over 4 hours
  2. customquenched with saturated aqueous NH4Cl
  3. extractionThe product was extracted into EtOAc (2×300 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography on silica (20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0d9608f8017d4f75b873bbbc2451b21a
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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