Water → benzyl (3R,4R)-1-((R)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)-4-hydroxypyrrolidin-3-ylcarbamate

HRID 338962노트

반응식

HRID 338962 반응식
FC(F)(F)S(O[C@@H:7]([C:12]1[CH:13]=[N:14][C:15]([Cl:18])=[CH:16][CH:17]=1)[C:8]([F:11])([F:10])[F:9])(=O)=O.[OH:21][C@@H:22]1[CH2:26][NH:25][CH2:24][C@H:23]1[NH:27][C:28](=[O:37])[O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C([O-])([O-])=O.[K+].[K+].O>C1COCC1.C(OCC)(=O)C>[Cl:18][C:15]1[N:14]=[CH:13][C:12]([C@@H:7]([N:25]2[CH2:26][C@@H:22]([OH:21])[C@H:23]([NH:27][C:28](=[O:37])[O:29][CH2:30][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:24]2)[C:8]([F:11])([F:10])[F:9])=[CH:17][CH:16]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 68219095Benzyl N-[(3R,4R)-4-hydroxypyrrolidin-3-YL]carbamateHCID 86707412(S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl trifluoromethanesulfonate

생성물 1

HCID 86707479benzyl (3R,4R)-1-((R)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)-4-hydroxypyrrolidin-3-ylcarbamate수율 59.2%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of (S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl trifluoromethanesulfonate (2.50 g, 7.28 mmol), benzyl (3R,4R)-4-hydroxypyrrolidin-3-ylcarbamate (2.41 g, 10.2 mmol) and K2CO3 (1.51 g, 10.9 mmol) in THF (40 mL) was stirred at 56° C. for 12 hours. Water (20 mL) and ethyl acetate (40 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (20:1 ethyl acetate/MeOH) to give benzyl (3R,4R)-1-((R)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)-4-hydroxypyrrolidin-3-ylcarbamate (1.85 g, 59.2%) as a solid.

후처리

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel (20:1 ethyl acetate/MeOH)

출처 및 근거

ORD 기록
ord-132b713e794b482b9b1bc39b7666ad3a
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889704B2

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