Triphenylphosphine → (1S,2S)-2-[4-((R)-4-Bromo-7-fluoro-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester

HRID 471437노트

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HRID 471437 반응식
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)=[O:5])[CH3:2].[Br:16][C:17]1[CH:25]=[CH:24][C:23]([F:26])=[C:22]2[C:18]=1[CH2:19][CH2:20][C@@H:21]2O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>O1CCCC1>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:10]=[CH:11][C:12]([O:15][C@H:21]2[C:22]3[C:18](=[C:17]([Br:16])[CH:25]=[CH:24][C:23]=3[F:26])[CH2:19][CH2:20]2)=[CH:13][CH:14]=1)=[O:5])[CH3:2]

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 72700607(1S,2S)-2-(4-Hydroxy-phenyl)-cyclopropanecarboxylic acid ethyl ester2회HCID 86697104(S)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-ol2회

생성물 1

HCID 86703877(1S,2S)-2-[4-((R)-4-Bromo-7-fluoro-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester수율 62.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-20 °C

실험 절차

(1S,2S)-2-(4-Hydroxy-phenyl)-cyclopropanecarboxylic acid ethyl ester (Intermediate 4, 6.51 g, 31.57 mmol), (S)-4-Bromo-7-fluoro-indan-1-ol (Intermediate 8, 7.29 g, 31.57 mmol) and triphenyl phosphine (9.11 g, 34.72 mmol) are dissolved in dry tetrahydrofuran (50 mL) and cooled to −20° C. under nitrogen atmosphere. Di-tert-butyl azodicarboxylate (8.00 g, 34.72 mmol) is added and the mixture stirred for 30 minutes at −20° C. then allowed to warm to room temperature and stirred overnight. The solvent is removed under vacuum and the residue purified by flash chromatography (0-10% ethyl acetate in cyclohexane) to give the title compound (Yield 8.23 g).

후처리

  1. temperatureto warm to room temperature
  2. stirringstirred overnight
  3. customThe solvent is removed under vacuum
  4. customthe residue purified by flash chromatography (0-10% ethyl acetate in cyclohexane)

출처 및 근거

ORD 기록
ord-64cb7b424d924751af225dc126914a08
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633182B2

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