(Diethylamino)sulfur trifluoride → 2-benzyl 1-tert-butyl (2R,3S)-3-fluoropyrrolidine-1,2-dicarboxylate

HRID 1527325노트

반응식

HRID 1527325 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10](O)[C@H:9]1[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(S(F)(F)[F:30])CC>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([F:30])[C@H:9]1[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

4

반응물 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 109252822-benzyl 1-tert-butyl (2S,3R)-3-hydroxypyrrolidine-1,2-dicarboxylate

생성물 1

HCID 155475702-benzyl 1-tert-butyl (2R,3S)-3-fluoropyrrolidine-1,2-dicarboxylate수율 89%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
-78 °C

실험 절차

The title compound was prepared in a similar manner as described by J. A. Hodges et al., J. Amer. Chem. Soc. 2005, 127, 15923-15932: To a solution of (2S,3R)-3-hydroxy-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (490 mg, 1.53 mmol) in CH2Cl2 (30 mL), cooled to −78° C., was added dropwise DAST (1.01 mL, 7.62 mmol). The reaction mixture was stirred at −78° C. for 5 h, and then was allowed to warm to RT and stirred overnight. After cooling to 0° C., the reaction was quenched with MeOH, followed by addition of aqueous NaHCO3 solution. Volatiles were removed under reduced pressure and the residue was taken up in EtOAc. The organics were washed with aqueous NaHCO3 (3×), water and brine, dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:9) to give the title compound (89% purity by HPLC/215 nm). MS (LC/MS): 346 [M+Na]+, 268 [MH−tBu]+, 224 [MH−Boc]+; tR (HPLC conditions b): 5.31 min.

후처리

  1. customThe title compound was prepared in a similar manner
  2. temperatureto warm to RT
  3. stirringstirred overnight
  4. temperatureAfter cooling to 0° C.
  5. customthe reaction was quenched with MeOH
  6. additionfollowed by addition of aqueous NaHCO3 solution
  7. customVolatiles were removed under reduced pressure
  8. washThe organics were washed with aqueous NaHCO3 (3×), water and brine
  9. customdried (Phase separator)
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:9)

출처 및 근거

ORD 기록
ord-dd1e78c5ed854ffdbace08515cfad80e
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085555B2

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