Methanol → HCID 67422338, compound

Temperature

5 °C

(1S,5R)-1-(3,4-Dichlorophenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one (22.6 g) was dissolved in 33% HBr/glacial acetic acid and heated to 80° C. for 5 h, cooled to rt and thrown into 1300 ml ice-water and stirred at rt for 16 h. The precipitated acid was isolated by filtration, redissolved in toluene (1000 ml), dried over anhydrous magnesium sulphate and evaporated in vacuo to give 30 g of the intermediate (1S,2R)-2-(bromomethyl)-1-(3,4-dichlorophenyl)cyclopropanecarboxylic acid. The (1S,2R)-2-(bromomethyl)-1-(3,4-dichlorophenyl)cyclopropanecarboxylic acid (30 g) was dissolved in anhydrous toluene (200 ml) and thionylchloride (18 ml) was added dropwise during 15 min. after which the mixture was refluxed for 60 min. The reaction mixture was cooled to 5° C. and methanol (200 ml) was added and the mixture was allowed to warm to rt and stirred at rt for 2 h. The mixture was evaporated in vacuo, redissolved in diethylether, washed with saturated aqueous sodium hydrogen carbonate 25 ml), brine (25 ml), dried over anhydrous magnesium sulphate and evaporated in vacuo. To give the intermediate (1S,2R)-2-(bromomethyl)-1-(3,4-dichlorophenyl)cyclopropanecarboxylic acid methyl ester (27 g). The (1S,2R)-2-(bromomethyl)-1-(3,4-dichlorophenyl)cyclopropanecarboxylic acid methyl ester (15 mmol) was dissolved in acetonitrile (50 ml) and added to a mixture an amine of formula III (15 mmol) in a mixture of acetonitrile (50 ml) and ethyl diisopropylamine (30 mmol). The mixture was stirred at room temperature for 16 h, evaporated in vacuo, taken up in ethyl acetate (200 ml) and washed successively with saturated sodium hydrogen carbonate (50 ml) and brine (50 ml, dried over anhydrous magnesium sulphate and evaporated in vacuo to give the crude product ester of formula VII. Esters of formula VII were generally purified by precipitation of the oxalate salt from acetone.

1. temperaturewas refluxed for 60 min
2. temperatureto warm to rt
3. customThe mixture was evaporated in vacuo
4. dissolutionredissolved in diethylether
5. washwashed with saturated aqueous sodium hydrogen carbonate 25 ml), brine (25 ml)
6. dry with materialdried over anhydrous magnesium sulphate
7. customevaporated in vacuo

ORD record

ord-d929a801762b44e2aed084e8eb3e53fd

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834008B2