Dicyclohexylcarbodiimide → N-methoxy-N-methyl-1-(trifluoromethyl)cyclopropane-1-carboxamide
Reaction equation
[F:1][C:2]([C:5]1([C:8]([OH:10])=O)[CH2:7][CH2:6]1)([F:4])[F:3].Cl.[CH3:12][O:13][NH:14][CH3:15].C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[CH3:12][O:13][N:14]([CH3:15])[C:8]([C:5]1([C:2]([F:4])([F:3])[F:1])[CH2:7][CH2:6]1)=[O:10]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
Trifluoromethyl cyclopropane carboxylic acid (500 mg, 3.24 mmol) was added to a freshly prepared solution of Weinreb amine (3.90 mmol) prepared by treating N-methoxymethanamine HCl salt with EtN-iPr2 (3.90 mmol) in CH2Cl2 at −40° C. and stirring for 5 min. DCC (801 mg, 3.90 mmol) in 5.0 mL of DCM was then added slowly over 3 min while cooling the solution at 0° C. The reaction mixture was stirred at RT for 48 h. It was then filtered through a plug of silica gel washing with Et2O. The volatiles were removed and the residue was purified on an ISCO 12 g column (20-70% EtOAc:Hexanes) to yield N-methoxy-N-methyl-1-(trifluoromethyl)cyclopropanecarboxamide (456 mg, 71% yield) as a clear colorless oil. A reference for this procedure could be found in: J. Org. Chem. 2005, 70, pages 5721-5724.
Workup
- customprepared
- stirringThe reaction mixture was stirred at RT for 48 h
- filtrationIt was then filtered through a plug of silica gel washing with Et2O
- customThe volatiles were removed
- customthe residue was purified on an ISCO 12 g column (20-70% EtOAc:Hexanes)
Sources & evidence
- ORD record
- ord-715b9bbc24ed4be18e83e2cf554c8d06
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08101612B2
Reaction notes
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