Diisopropylcarbodiimide → Tert-butyl 1-(4-(5-(((1-(4-fluorophenyl)cyclohexyl)methoxy)methyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

HRID 71267노트

반응식

HRID 71267 반응식
C(N=C=NC(C)C)(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2([CH2:23][O:24][CH2:25][C:26]([OH:28])=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:13][CH:12]=1.[C:29]([O:33][C:34]([CH:36]1[CH2:39][N:38]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([C:47](=[N:49]O)[NH2:48])=[CH:43][CH:42]=2)[CH2:37]1)=[O:35])([CH3:32])([CH3:31])[CH3:30].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>ClCCl>[F:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2([CH2:23][O:24][CH2:25][C:26]3[O:28][N:49]=[C:47]([C:44]4[CH:43]=[CH:42][C:41]([CH2:40][N:38]5[CH2:37][CH:36]([C:34]([O:33][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:35])[CH2:39]5)=[CH:46][CH:45]=4)[N:48]=3)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]2)=[CH:15][CH:16]=1

참가 물질

6

반응물 4

HCID 12734DiisopropylcarbodiimideHCID 2724141Tetrabutylammonium FluorideHCID 666856282-((1-(4-Fluorophenyl)cyclohexyl)methoxy)acetic acidHCID 76806751tert-butyl 1-[[4-(N'-hydroxycarbamimidoyl)phenyl]methyl]azetidine-3-carboxylate

생성물 1

HCID 66692288Tert-butyl 1-(4-(5-(((1-(4-fluorophenyl)cyclohexyl)methoxy)methyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate수율 64%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

N,N′-Diisopropylcarbodiimide (17 mg, 135 μmol) was added to a stirred solution of crude 2-((1-(4-fluorophenyl)cyclohexyl)methoxy)acetic acid (30 mg, 113 μmol) and tert-butyl-1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (34 mg, 113 μmol) in dichloromethane (1.5 mL). The reaction mixture was stirred at room temperature for 40 min and concentrated. The residue was diluted with acetonitrile (1.5 mL) and treated with a 1 M solution of tetra-n-butylammonium fluoride (113 μL, 113 μmol). The mixture was stirred at room temperature for 16 h and concentrated. The crude residue was chromatographed on silica gel (Teledyne-Isco RediSep 12 g column), and eluted with 10%, 20% and 30% EtOAc in hexanes to obtain tert-butyl 1-(4-(5-(((1-(4-fluorophenyl)cyclohexyl)methoxy)methyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (38.5 mg, 64% yield) as a viscous colorless oil.

후처리

  1. concentrationconcentrated
  2. additionThe residue was diluted with acetonitrile (1.5 mL)
  3. stirringThe mixture was stirred at room temperature for 16 h
  4. concentrationconcentrated
  5. customThe crude residue was chromatographed on silica gel (Teledyne-Isco RediSep 12 g column)
  6. washeluted with 10%, 20% and 30% EtOAc in hexanes

출처 및 근거

ORD 기록
ord-6759b56f13454c32a98206150005a3d6
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822510B2

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