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

HRID 71267Notes

Reaction equation

HRID 71267 reaction equation
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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-6759b56f13454c32a98206150005a3d6
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Reaction notes

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