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Diisopropylethylamine → tert-butyl (1R,3R,4S)-3-(methoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamate

HRID 2225246
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HRID 2225246 반응식
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@@H:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][C@H:3]1[CH2:16][O:17][CH3:18].[F:19][C:20]([F:35])([F:34])[C:21]1[CH:22]=[C:23]([CH:31]=[CH:32][CH:33]=1)[C:24]([NH:26][CH2:27][C:28](O)=[O:29])=[O:25].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(#N)C.C(OCC)(=O)C>[CH3:18][O:17][CH2:16][C@H:3]1[C@@H:2]([NH:1][C:28](=[O:29])[CH2:27][NH:26][C:24](=[O:25])[C:23]2[CH:31]=[CH:32][CH:33]=[C:21]([C:20]([F:19])([F:35])[F:34])[CH:22]=2)[CH2:7][CH2:6][C@@H:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14])[CH2:4]1
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참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 2777432((3-(Trifluoromethyl)benzoyl)amino)acetic acidHCID 68765639tert-butyl (1R,3R,4S)-4-amino-3-(methoxymethyl)cyclohexylcarbamate

생성물 1

HCID 86596947tert-butyl (1R,3R,4S)-3-(methoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamate
수율 60.4%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of tert-butyl (1R,3R,4S)-4-amino-3-(methoxymethyl)cyclohexylcarbamate (45 mg, assumed 0.163 mmol) in acetonitrile (1.5 mL) was treated sequentially with 2-(3-(trifluoromethyl)benzamido)acetic acid (43 mg, 0.174 mmol, see PCT WO 0250019), diisopropylethylamine (61 μL, 0.348 mmol) and TBTU (62 mg, 0.192 mmol). The mixture was stirred at rt for 2.75 h, then was diluted with ethyl acetate, washed sequentially with 1.0 M aqueous HCl, saturated aqueous NaHCO3, water and brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel, eluting with 1:3 v/v hexane-ethyl acetate, to provide tert-butyl (1R,3R,4S)-3-(methoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamate as a white solid (48 mg). MS found: (M+H)+=488.3.

후처리

  1. washwashed sequentially with 1.0 M aqueous HCl, saturated aqueous NaHCO3, water and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by flash column chromatography on silica gel
  5. washeluting with 1:3 v/v hexane-ethyl acetate

출처 및 근거

ORD 기록
ord-e4f72adb51064f89bff319026b14b724
출처 데이터셋
uspto-grants-2008_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07378409B2

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