Methanesulfonyl chloride → (R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidine-1-carboxylate

HRID 1426895노트

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HRID 1426895 반응식
[Si:1]([O:8][C@H:9]([CH2:19][CH:20]([C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[O:29][CH3:30])O)[CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CS(Cl)(=O)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Si:1]([O:8][CH:9]1[CH2:10][N:11]([C:12]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:18])[C@@H:20]([C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=2[O:29][CH3:30])[CH2:19]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

참가 물질

5

반응물 3

HCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 67470707(R)-tert-butyl 2-(tert-butyldimethylsilyloxy)-4-(5-fluoro-2-methoxyphenyl)-4-hydroxybutylcarbamate

생성물 1

HCID 67470718(R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidine-1-carboxylate수율 57.38%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
-5 °C

실험 절차

To a solution of (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)-4-(5-fluoro-2-methoxyphenyl)-4-hydroxybutylcarbamate (4.810 g, 10.84 mmol) in CH2Cl2 (108 mL) at −60° C. was added TEA (4.534 mL, 32.53 mmol) followed by methanesulfonyl chloride (0.9231 mL, 11.93 mmol). The resulting mixture was slowly warmed to −5° C. and poured into a mixture of ice and saturated aqueous NaHCO3 (50 mL). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (2×50 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica column chromatography, eluting with 2-10% MeOH/DCM to afford (R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidine-1-carboxylate (assumed to be a mixture of cis and trans isomers; 2.648 g, 57.38% yield). LC/MS (ES+APCI) m/z=326.1 (M+H-Boc).

후처리

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with CH2Cl2 (2×50 mL)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give the crude material that
  7. customwas purified by silica column chromatography
  8. washeluting with 2-10% MeOH/DCM

출처 및 근거

ORD 기록
ord-8acb7243285b477bb3397201b1b63129
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08933084B2

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