反应详情

A solution of (9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid, prepared as in Example 11 (1.25 g, 4.61 mmol) in dichloromethane (20 mL) was treated with oxalyl chloride (731 mg, 5.76 mmol) and N,N-dimethylformamide (10 mg, 0.14 mmol). The resulting solution was warmed to reflux temperature for 2 h, then was cooled to room temperature and the excess reagent was evaporated in vacuo. The residue was dissolved in tetrahydrofuran (10 mL) and added dropwise to a solution of (R*)-1-(4-piperidyl)-1-(3-pyridyl)ethanol (950 mg, 4.61 mmol) and triethylamine (582 mg, 5.76 mmol) in tetrahydrofuran (15 mL) and dichloromethane (25 mL). The resulting mixture was stirred for 3 h at room temperature, then was poured into 1N aqueous sodium hydroxide (25 mL) and extracted with chloroform (3×100 mL) The organic extracts were washed sequentially with 1N aqueous sodium hydroxide (50 mL) and brine (50 mL), combined, dried over sodium sulfate, filtered and evaporated to leave a dark tan foam. Purification by flash chromatography (eluant: 1:1 hexane/acetone) afforded the title amide as an off white foam (2.00 g, 4.36 mmol, 95%). CIMS: m/z 461 ((M+H)+, 37Cl, 33%), 460 ((M+H+1)+, 35Cl, 28), 459 ((M+M)+, 35Cl, 100).

1. temperatureThe resulting solution was warmed
2. temperatureto reflux temperature for 2 h
3. customthe excess reagent was evaporated in vacuo
4. dissolutionThe residue was dissolved in tetrahydrofuran (10 mL)
5. extractionextracted with chloroform (3×100 mL) The organic extracts
6. washwere washed sequentially with 1N aqueous sodium hydroxide (50 mL) and brine (50 mL)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. customevaporated
10. customto leave a dark tan foam
11. customPurification by flash chromatography (eluant: 1:1 hexane/acetone)