Potassium bis(trimethylsilyl)amide → (2R,3R)-1-benzyl 4-tert-butyl 3-(3-methylisoxazol-4-yl)-2-(3,3,3-trifluoropropyl)succinate

HRID 2276877노트

반응식

HRID 2276877 반응식
[CH3:1][C:2]1[C:6]([CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[CH:5][O:4][N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:25][C:26]([F:49])([F:48])[CH2:27][CH2:28][C@@H:29](OS(C(F)(F)F)(=O)=O)[C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31]>C1COCC1.C1(C)C=CC=CC=1>[CH3:1][C:2]1[C:6]([C@H:7]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@@H:29]([CH2:28][CH2:27][C:26]([F:25])([F:48])[F:49])[C:30]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:31])=[CH:5][O:4][N:3]=1

참가 물질

6

반응물 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 90079932Tert-butyl 2-(3-methylisoxazol-4-yl)acetateHCID 90086998(R)-benzyl 5,5,5-trifluoro-2-(trifluoromethylsulfonyloxy)pentanoate

생성물 1

HCID 90079887(2R,3R)-1-benzyl 4-tert-butyl 3-(3-methylisoxazol-4-yl)-2-(3,3,3-trifluoropropyl)succinate수율 61.1%

시약·촉매·용매 2

HCID 1140Toluene용매2회HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
-78 °C

실험 절차

In a 250 mL round-bottomed flask a solution of tert-butyl 2-(3-methylisoxazol-4-yl)acetate (1.75 g, 8.87 mmol) in THF (56 mL) and toluene (27 mL) was cooled in −78° C. bath and treated with a solution of 1M KHMDS (11.09 mL, 11.09 mmol) in THF dropwise over 2 minutes via syringe. After stirring for 15 minutes at −78° C., the reaction mixture was placed in a room temperature water bath for 15 minutes and then again in −78° C. bath for another 15 minutes before a solution of Preparation 4D (R)-benzyl 5,5,5-trifluoro-2-(trifluoromethylsulfonyloxy)pentanoate (4.55 g, 11.53 mmol) in 6 mL THF and 3 mL toluene was added to the reaction over 2 minutes. The reaction mixture was stirred in −78° C. bath for 2 hours before being quenched with saturated aqueous NH4Cl and then warmed to room temperature. The mixture was diluted with brine and extracted with EtOAc. The organic layer was dried over MgSO4 filtered and concentrated. The residue was purified on silica gel column (330 g ISCO) eluting with a gradient of 0-30% EtOAc/CH2Cl2, and collected tubes containing product were concentrated to give (2R,3R)-1-benzyl 4-tert-butyl 3-(3-methylisoxazol-4-yl)-2-(3,3,3-trifluoropropyl)succinate (2.394 g, 61% yield) containing about 30% of the (2R,3S) isomer.

후처리

  1. customwas placed in a room temperature
  2. customfor 15 minutes
  3. additionwas added to the reaction over 2 minutes
  4. stirringThe reaction mixture was stirred in −78° C. bath for 2 hours
  5. custombefore being quenched with saturated aqueous NH4Cl
  6. temperaturewarmed to room temperature
  7. additionThe mixture was diluted with brine
  8. extractionextracted with EtOAc
  9. dry with materialThe organic layer was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified on silica gel column (330 g ISCO)
  13. washeluting with a gradient of 0-30% EtOAc/CH2Cl2
  14. customcollected tubes
  15. additioncontaining product
  16. concentrationwere concentrated

출처 및 근거

ORD 기록
ord-29b99e0b8d31428aba53a74e1b16fd64
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133139B2

반응 노트

불러오는 중…