Acetone cardice → 2-(4-Cyclohexyloxy-phenyl)-1-cyclopropyl-ethanone
Reaction equation
[CH:1]1([O:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C:15](N(OC)C)=[O:16])=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:21]1([Mg]Br)[CH2:23][CH2:22]1.C(=O)=O.CC(C)=O>C1COCC1>[CH:1]1([O:7][C:8]2[CH:9]=[CH:10][C:11]([CH2:14][C:15]([CH:21]3[CH2:23][CH2:22]3)=[O:16])=[CH:12][CH:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1Participants
Conditions
- Temperature
- -78 °C
Procedure
To a stirred solution of 2-(4-cyclohexyloxy-phenyl)-N-methoxy-N-methyl-acetamide (Example 14, 1.31 mmol, 0.36 g) in anhydrous THF (1 mL) at −78° C. was added cyclopropylmagnesium bromide (2 M in diethyl ether, 2.62 mmol, 5.25 mL) dropwise over 5 minutes. The reaction was stirred for 30 minutes at −78° C. The dry ice/acetone bath was replaced with an ice bath and the reaction was stirred for an additional 30 min. The reaction mixture was quenched by addition of saturated ammonium chloride (5 mL) and extracted with ethyl acetate (2×10 mL). The combined ethyl acetate layers were washed with brine (5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a 12 g SiO2 column with 6-8% ethyl acetate in hexanes to give 2-(4-cyclohexyloxy-phenyl)-1-cyclopropyl-ethanone (0.24 g).
Workup
- stirringthe reaction was stirred for an additional 30 min
- customThe reaction mixture was quenched by addition of saturated ammonium chloride (5 mL)
- extractionextracted with ethyl acetate (2×10 mL)
- washThe combined ethyl acetate layers were washed with brine (5 mL)
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified on a 12 g SiO2 column with 6-8% ethyl acetate in hexanes
Sources & evidence
- ORD record
- ord-dba47098be3f426781a3d4d7c386c683
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08431575B2
Reaction notes
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