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Methanol → Tert-butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(2-fluorophenyl)piperidine-1-carboxylate

HRID 391462
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HRID 391462 반응식
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([CH2:12]Br)[CH:3]=1.[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21]1([CH2:34][OH:35])[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]1.CC(C)([O-])C.[K+].CO>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1)[CH2:12][O:35][CH2:34][C:21]1([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[F:14])[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26]1
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참가 물질

6

반응물 4

HCID 887Methanol2회HCID 223242723-Bromo-5-(trifluoromethyl)benzyl bromideHCID 23665647Potassium tert-butoxide2회HCID 58993673Tert-butyl 4-(2-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate

생성물 1

HCID 58993612Tert-butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(2-fluorophenyl)piperidine-1-carboxylate

시약·촉매·용매

1
HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

A flask was charged with 1-bromo-3-(bromomethyl)-5-(trifluoromethyl)benzene (0.149 g, 0.47 mmol) and tert-butyl 4-(2-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (0.112 g, 0.36 mmol) in tetrahydrofuran (2 mL) at 0° C. The reaction was treated with potassium tert-butoxide (0.41 mg, 0.36 mmol), stirred at 0° C. for 20 min, and treated with another aliquot of potassium tert-butoxide (0.41 mg, 0.36 mmol). The reaction was allowed to warm to room temperature and was stirred for 16 h. The reaction mixture was evaporated in vacuo and the crude oil was purified by silica gel chromatography (5% ethyl acetate/95% hexanes→30% ethyl acetate/70% hexanes) to afford 0.138 g (70%) of the desired ether. Mass spec.: 546.03 (MH)+ LC tr=4.501 min. (Phenomenex-Luna 4.6×50 mm S10, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA Gradient Time=4 min, Flow rate=4 mL/min).

후처리

  1. temperatureto warm to room temperature
  2. stirringwas stirred for 16 h
  3. customThe reaction mixture was evaporated in vacuo
  4. customthe crude oil was purified by silica gel chromatography (5% ethyl acetate/95% hexanes→30% ethyl acetate/70% hexanes)
  5. customto afford 0.138 g (70%) of the desired ether

출처 및 근거

ORD 기록
ord-e57606b6137d413cac4ff10b1abd9223
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08383821B2

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