(2R)-Oxiran-2-ylmethyl butanoate → HCID 21462612, compound

HRID 266710

Reaction equation

HRID 266710 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 21462612HCID 21462612, compoundYield 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 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 added 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-e202df859727451f9225014e2f35f7a8
Source dataset
uspto-grants-1997_07
Patent number
US05652238

Linked notes

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