Water → (+/-)-tert-Butyl 1-[(3-bromo-4-chlorophenyl)(methoxy)methyl]cyclopropanecarboxylate
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]([OH:20])[C:10]2([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:12][CH2:11]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:21]I.[H-].[Na+].O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:9]([O:20][CH3:21])[C:10]2([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:11][CH2:12]2)[CH:5]=[CH:6][C:7]=1[Cl:8]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
16.0 g (44.2 mmol) of (+/−)-tert-butyl 1-[(3-bromo-4-chlorophenyl)(hydroxy)methyl]cyclopropanecarboxylate were dissolved in 80 ml of DMF, and 4.1 ml (66.6 mmol) of methyl iodide were added at RT. The reaction mixture was cooled to +10° C., and 1.95 g (60% in mineral oil, 48.7 mmol) of sodium hydride were added in several portions. Ten minutes after the addition had ended, the mixture was warmed to RT and stirred at RT for a further 1.5 h. The reaction mixture was then added to water and extracted three times with ethyl acetate. The combined organic phases were concentrated under reduced pressure and the residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1). This gave 15.3 g of the target compound (92.2% of theory).
Workup
- temperatureThe reaction mixture was cooled to +10° C.
- additionTen minutes after the addition
- extractionextracted three times with ethyl acetate
- concentrationThe combined organic phases were concentrated under reduced pressure
- customthe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1)
Sources & evidence
- ORD record
- ord-e5093d539e8c4538a7fd4734d28d33ed
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09018258B2
Reaction notes
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