反应详情

A mixture of 28.9 g (125 mmoles) of 2-butyl-1,3-diazaspiro[4.4]nonan-4-one, hydrochloride, 1.3 mL of 75% aqueous solution of methyl tributylammonium chloride, 90 mL (10 N) of 33% aqueous sodium hydroxide and 90 mL of methylene chloride was vigorously stirred for 5 minutes at room temperature and then cooled to 7-12° C. To this vigorously stirred cooled mixture at 7-12° C. was added a solution of 36.04 g (132 mmoles, amount determined quantitatively by HPLC) in 300 mL of methylene chloride of 4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile over a period of 70 minutes. After that, the reaction mixture was allowed to warm up to room temperature and stirred additionally at room temperature for a half hour. Then the phases were separated and the organic phase was washed twice with 90 mL of water. The organic phase was concentrated under reduced pressure to the minimum agitation volume, and methyl tertiarybutyl ether was added. Concentration was continued to displace the dichloromethane, and the product was crystallized from the methyl tertiarybutyl ether solution. The crystals were collected on a filter, washed with cold 120 ml of methyl-tertiarybutyl ether and dried in a vacuum oven at 40° C. and a pressure of 3.1 mm Hg to give 39.9 g (82.4%) of the title compound having a laboratory HPLC of HI 99.8.

1. temperaturecooled to 7-12° C
2. stirringTo this vigorously stirred
3. temperaturecooled mixture at 7-12° C.
4. additionwas added a solution of 36.04 g (132 mmoles, amount
5. customof 70 minutes
6. temperatureto warm up to room temperature
7. stirringstirred additionally at room temperature for a half hour
8. customThen the phases were separated
9. washthe organic phase was washed twice with 90 mL of water
10. concentrationThe organic phase was concentrated under reduced pressure to the minimum agitation volume, and methyl tertiarybutyl ether
11. additionwas added
12. concentrationConcentration
13. customthe product was crystallized from the methyl tertiarybutyl ether solution
14. customThe crystals were collected on a filter
15. washwashed with cold 120 ml of methyl-tertiarybutyl ether
16. customdried in a vacuum oven at 40° C.