Water → HCID 86638598, compound

To a suspension of sodium hydride (200 mg, 8.33 mmol) in anhydrous dimethylformamide (20 mL) was added a solution of (1R,2R)/(1S,2S)-2-(1,4-dioxa-7-azaspiro[4.4]non-7-yl)cyclohexanol (1.5 g, 6.6 mmol) in anhydrous dimethylformamide (10 mL). The resulting mixture was stirred at room temperature for 30 min. and then a solution of 3-(cyclohexyl)propyl bromide (1.67 g, 8.15 mmols) in anhydrous dimethylformamide was quickly added. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water (200 mL) and then extracted with ethyl acetate (3×50 mL). The combined organic extracts were back-washed with brine (50 mL) and the solvent was evaporated in vacuo. The residue was taken up with water (50 mL) and the pH was adjusted to pH 1.0 with 6M HCl aqueous solution. The acidic aqueous solution was extracted with diethyl ether (2×50 mL), then basified to pH 5.0-5.5 with 5M NaOH aqueous solution and extracted with diethyl ether (3×50 mL). The combined organic extracts at pH 5.0-5.5 were concentrated in vacuo to provide the crude title compound suitable for the next step without any further purification.

1. stirringThe reaction mixture was stirred at room temperature for 16 hours
2. extractionextracted with ethyl acetate (3×50 mL)
3. washThe combined organic extracts were back-washed with brine (50 mL)
4. customthe solvent was evaporated in vacuo
5. extractionThe acidic aqueous solution was extracted with diethyl ether (2×50 mL)
6. extractionextracted with diethyl ether (3×50 mL)
7. concentrationThe combined organic extracts at pH 5.0-5.5 were concentrated in vacuo

ORD record

ord-eee44ac5d56b4b87b77c890dd3c61c8b

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008342B2