Ethanol → (7R)-7-(4-Bromophenyl)-1,3-diazaspiro[4.4]nonane-2,4-dione

Temperature

80 °C

To a mixture of (R)-3-(4-bromophenyl)cyclopentanone (I-2A, 5.4 g, 22.58 mmol) and potassium cyanide (2.132 g, 32.7 mmol) in EtOH (40 mL) and water (20 mL) in a glass pressure vessel was added ammonium carbonate (5.42 g, 56.5 mmol). The reaction vessel was sealed and placed in an oil bath heated at 80° C. for 20 hours. A large amount of white, free flowing solid formed in the pale yellow solution. Analysis by LCMS indicated remaining starting material so the reaction was continued for an additional 24 hours. As conversion was incomplete, the temperature of the oil bath was raised to 120° C. The white solid completely dissolved at the higher temperature. After 3 hours the solution was cooled down to room temperature. The solution was further cooled in an ice bath, water (30 mL) was added and the resulting white solid was collected by filtration, washed with water, air dried, then placed under high vacuum to afford the target compound (6.9 g, 22.32 mmol) which was used for subsequent reaction without additional purification. HPLC retention time=0.81 min (Condition G); LC/MS MH=309/311; 2M+H=619.

1. customThe reaction vessel was sealed
2. customplaced in an oil bath
3. customformed in the pale yellow solution
4. temperaturethe temperature of the oil bath was raised to 120° C
5. dissolutionThe white solid completely dissolved at the higher temperature
6. temperatureAfter 3 hours the solution was cooled down to room temperature
7. temperatureThe solution was further cooled in an ice bath
8. filtrationthe resulting white solid was collected by filtration
9. washwashed with water, air
10. customdried

ORD record

ord-bbc6e9cf64c14a5f82c79339601cde08

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115054B2