(2R)-Oxiran-2-ylmethyl butanoate → [3-[3,5-Difluoro-4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methanol

HRID 1940650

Reaction equation

HRID 1940650 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([F:20])=[CH:18][C:17]([NH:21][C:22](OCC3C=CC=CC=3)=O)=[CH:16][C:15]=2[F:32])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)=O.CC(C)=O.[Li]CCCC.[CH2:45]([O:49][C:50](=[O:54])CCC)[C@@H:46]1[O:48]C1>C1COCC1.C(Cl)Cl.CO.C(Cl)(Cl)Cl>[F:20][C:19]1[CH:18]=[C:17]([N:21]2[CH2:22][CH:45]([CH2:46][OH:48])[O:49][C:50]2=[O:54])[CH:16]=[C:15]([F:32])[C:14]=1[N:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]1

Participants

8

Reactant 4

HCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 18522661Acetone cardiceHCID 214626171-(Tert-butoxycarbonyl)-4-[2,6-difluoro-4-(benzyloxycarbonyl)aminophenyl]piperazineHCID 178418339Butyllithium

Product 1

HCID 21462612[3-[3,5-Difluoro-4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methanolYield 86.3%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
-78 °C

Procedure

The 1-(tert-butoxycarbonyl)-4-[2,6-difluoro-4-(benzyloxycarbonyl)aminophenyl]piperazine (14.05 g, 31 mmol) was dissolved in dry THF (150 mL) and then cooled to -78° C. (dry ice/acetone). The reaction was next treated with n-BuLi (21.6 mL, 35 mmol) dropwise over a 25 minute period. The reaction was allowed to stir at -78° C. for 30 minutes and then (R)-(-)-glycidylbutyrate (4.89 mL, 35 mmol) was dropwise over 7 minutes. The reaction was maintained at -78° C. for an additional 15 minutes and then the bath was removed, allowing the reaction to slowly warm up to room temperature overnight. The reaction was determined to be complete by TLC (5% MeOH/CHCl3, UV short wave). The reaction mixture was diluted with 500 mL CH2Cl2 and then washed with both H2O (3×300 mL) and brine (300 mL). The aqueous portions were back-extracted with more CH2Cl2 (3×400 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to give a creamy yellow solid. The crude solid was purified by recrystallization from hot EtOAc/hexane to give 11.063 g (85%) of the title compound as a white solid with mp 164°-166° C.

Workup

  1. temperatureThe reaction was maintained at -78° C. for an additional 15 minutes
  2. customthe bath was removed
  3. customthe reaction
  4. temperatureto slowly warm up to room temperature overnight
  5. washwashed with both H2O (3×300 mL) and brine (300 mL)
  6. extractionThe aqueous portions were back-extracted with more CH2Cl2 (3×400 mL)
  7. dry with materialThe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a creamy yellow solid
  11. customThe crude solid was purified by recrystallization from hot EtOAc/hexane

Sources & evidence

ORD record
ord-f656e2f3ee2c483c9850f7746f50fcdf
Source dataset
uspto-grants-1997_12
Patent number
US05700799

Linked notes

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