Methyl Ethyl Ketone → (1S,2S)-2-(3-Ketopyrrolidinyl)-1-[3-(Cyclohexyl)Propoxy]Cyclohexane Monohydrochloride

(1R,2S)/(1S,2R)-2-(3-Ketopyrrolidinyl)-1-[3-(cyclohexyl)propoxy]cyclohexane monohydrochloride: (1R,2R)/(1S,2S)-2-[1,4-Dioxa-7-azaspiro[4.4]non-7-yl]-1-[3-(cyclohexyl)propoxy]cyclohexane (ii) in a mixture of 6M HCl aqueous solution-butanone (1:4, v/v, 100 mL) was refluxed for 16 hours. The cooled reaction mixture was concentrated in vacuo and the residual aqueous solution was diluted with water (˜50 mL). The acidic aqueous solution was extracted with diethyl ether (50 mL) and then with dichloromethane (3×50 mL). The dichloromethane extracts were dried over sodium sulfate and the solvent was evaporated in vacuo to provide the crude title compound. The hydrochloride salt was crystallized by triturating in a mixture of diethyl ether-hexanes (1:1, v/v, ˜200 mL) and then precipitated from a mixture of dichloromethane-diethyl ether-hexanes to yield 0.8 g of the title compound, having the elemental analysis indicated in Table 1.

1. temperaturewas refluxed for 16 hours
2. customThe cooled reaction mixture
3. concentrationwas concentrated in vacuo
4. additionthe residual aqueous solution was diluted with water (˜50 mL)
5. extractionThe acidic aqueous solution was extracted with diethyl ether (50 mL)
6. dry with materialThe dichloromethane extracts were dried over sodium sulfate
7. customthe solvent was evaporated in vacuo
8. customto provide the crude title compound
9. customThe hydrochloride salt was crystallized
10. customby triturating in a mixture of diethyl ether-hexanes (1:1, v/v, ˜200 mL)
11. customprecipitated from a mixture of dichloromethane-diethyl ether-hexanes

ORD record

ord-8e8c1873a0924e4fad54f4e5ef7b3e0d

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07875611B2