Pyridine → methyl 3-(S)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-ylcarbonyl)-2-(R)-fluoropropionate

HRID 1008285노트

반응식

HRID 1008285 반응식
[CH2:1]([C@@H:5]([C:12]([N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:13])[C@H:6](O)[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH2:3][CH3:4].N1C=CC=CC=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)[F:36])(=O)=O>C(Cl)Cl>[CH2:1]([C@@H:5]([C:12]([N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:13])[C@@H:6]([F:36])[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH2:3][CH3:4]

참가 물질

5

반응물 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 59908531methyl 3-(R)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-yl-carbonyl)-2-(S)-hydroxypropionate

생성물 1

HCID 59908476methyl 3-(S)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-ylcarbonyl)-2-(R)-fluoropropionate수율 45%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
-20 °C

실험 절차

To methyl 3-(R)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-ylcarbonyl)-2-(S)-hydroxypropionate G-3 (5 mmol) in DCM (5 mL) was added pyridine (15 mmol), the reaction was cooled to −20° C., then triflic anhydride was added (7.5 mmol). The solution was stirred for 1 hour, then washed with aqueous citric acid, sodium bicarbonate and brine, then dried (Na2SO4) and concentrated. The intermediate triflate was then resuspended in DCM and cooled to −50° C. Tris(dimethylamino)sulfur (trimethylsilyl)difluoride (TAS-F) was added (5 mmol) and the solution allowed to warm to rt. The reaction mixture was washed with aqueous sodium bicarbonate and brine, dried (Na2SO4) and concentrated then purified on silica gel (ethylacetate/hexanes) to afford 2.3 mmol (45%) of methyl 3-(S)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-yl-carbonyl)-2-(R)-fluoropropionate G-4.

후처리

  1. washwashed with aqueous citric acid, sodium bicarbonate and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. temperaturecooled to −50° C
  5. additionTris(dimethylamino)sulfur (trimethylsilyl)difluoride (TAS-F) was added (5 mmol)
  6. temperatureto warm to rt
  7. washThe reaction mixture was washed with aqueous sodium bicarbonate and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customthen purified on silica gel (ethylacetate/hexanes)

출처 및 근거

ORD 기록
ord-84fb141af9a14f8ab8616a1ed0fc70ff
출처 데이터셋
uspto-grants-2004_09
특허 번호
US06797820B2

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