Sodium hydride → tert-butyl (S)-3-(2-bromo-5-fluorobenzyloxy)pyrrolidine-1-carboxylate

HRID 928070노트

반응식

HRID 928070 반응식
[H-].[Na+].[OH:3][C@H:4]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]1.[Br:16][C:17]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:18]=1[CH2:19]Br>C1COCC1>[Br:16][C:17]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:18]=1[CH2:19][O:3][C@H:4]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 5179721-Bromo-2-(bromomethyl)-4-fluorobenzeneHCID 854055tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylate

생성물 1

HCID 68923111tert-butyl (S)-3-(2-bromo-5-fluorobenzyloxy)pyrrolidine-1-carboxylate수율 100.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

Sodium hydride (60% oil dispersion, 0.24 g) was added to a stirred solution of tert-butyl (S)-3-hydroxypyrrolidine-1-carboxylate (0.935 g) in THF (15 mL) and the mixture was stirred for 5 minutes. 2-Bromo-5-fluorobenzyl bromide (1.608 g) was added and stirring was continued for 20 hours. The resultant suspension was filtered and the filtrate was evaporated to dryness. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-15% to give tert-butyl (S)-3-(2-bromo-5-fluorobenzyloxy)-pyrrolidine-1-carboxylate (1.88 g) as a colourless oil.

후처리

  1. stirringstirring
  2. waitwas continued for 20 hours
  3. filtrationThe resultant suspension was filtered
  4. customthe filtrate was evaporated to dryness
  5. customThe residue was purified by chromatography on silica
  6. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-15%

출처 및 근거

ORD 기록
ord-fc74d8ab5ee94ea7b305504110d3b307
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290472B2

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