Hydrochloric Acid → (4S)-4-benzyl-3-[(2R)-2-[[4-(trifluoromethyl)phenyl]methyl]butanoyl]oxazolidin-2-one

HRID 1500232Notes

Reaction equation

HRID 1500232 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:18])[CH2:15][CH2:16][CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[F:29][C:30]([F:40])([F:39])[C:31]1[CH:38]=[CH:37][C:34]([CH2:35]Br)=[CH:33][CH:32]=1.Cl>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:18])[C@@H:15]([CH2:35][C:34]1[CH:33]=[CH:32][C:31]([C:30]([F:29])([F:39])[F:40])=[CH:38][CH:37]=1)[CH2:16][CH3:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 11010277(S)-4-benzyl-3-butyryloxazolidin-2-one

Product 1

HCID 90137163(4S)-4-benzyl-3-[(2R)-2-[[4-(trifluoromethyl)phenyl]methyl]butanoyl]oxazolidin-2-oneYield 61.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-68 °C

Procedure

To a 3-necked 5 L RBF is added THF (2 L) and (4S)-4-benzyl-3-butanoyl-oxazolidin-2-one (270 g 1.09 moles) under N2. The resulting solution is cooled to −68° C. in an acetone-dry ice bath. To the cold solution is added sodium bis(trimethylsilyl)amide (1320 mL of 1M THF solution; 1.32 moles) dropwise over 1.5 h while the internal temperature is held between −68 to −60° C. Upon completion of the addition, the reaction is stirred at −68° C. for 30 min. To the cold solution is then added 4-trifluoromethylbenzyl bromide (278 g; 1.16 moles) in THF (1 L) over 30 min at −68° C. After 1.5 h, the reaction is poured into 1 M HCl. The mixture is extracted with ethyl acetate (3 L×1). The extracts are combined and washed with aq. NaHCO3 (2 L×1) and brine (2 L×1). The organic phase is dried over Na2SO4, filtered, and concentrated. The solid is triturated with EtOH (600 mL) at 15° C. Filtration provides the title compound as a solid (270 g, MS:[M+H]+=406 m/z).

Workup

  1. customis held between −68 to −60° C
  2. additionUpon completion of the addition
  3. waitAfter 1.5 h
  4. extractionThe mixture is extracted with ethyl acetate (3 L×1)
  5. washwashed with aq. NaHCO3 (2 L×1) and brine (2 L×1)
  6. dry with materialThe organic phase is dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe solid is triturated with EtOH (600 mL) at 15° C
  10. filtrationFiltration

Sources & evidence

ORD record
ord-1b48a5c654544aceba0a89b6194945df
Source dataset
uspto-grants-2015_12
Patent number
US09206139B2

Reaction notes

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