Boron trifluoride → HCID 58550953, compound

Temperature

0 °C

To a solution of triethyl orthoformate (71 mL, 0.43 mol)] in dichloromethane (250 mL) at −10° C. under nitrogen was added boron trifluoride diethyletherate (54 mL, 0.43 mol) dropwise over 30 minutes. The mixture was allowed to warm to 0° C. and stirring was continued at 0° C. for 15 minutes. The mixture was then cooled to −78° C. and a solution of benzyl 4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (50 g, 0.14 mol) in dichloromethane (250 mL) was added dropwise over 1 hour, followed by N-ethyl-N-isopropylpropan-2-amine (87 mL, 0.50 mol) over 1 hour at −78° C. The mixture was continued to stir at −78° C. for 30 minutes and then at 25° C. for 15 hours. The reaction mixture was diluted with dichloromethane (750 mL) and then partitioned with saturated sodium bicarbonate solution (500 mL). The organic phase was washed with water (500 mL), saturated sodium chloride solution (500 mL), dried over magnesium sulfate and concentrated under reduced pressure. Purification by silica gel flash chromatography (0-50% ethyl acetate in hexane) afforded benzyl 3-(diethoxymethyl)-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (50 g, 78%) as a yellow oil. ESI-MS m/z calc. 453.2, found 408.5 (M+1-OEt)+; Retention time: 2.08 minutes (3 min run).

1. temperatureThe mixture was then cooled to −78° C.
2. stirringto stir at −78° C. for 30 minutes
3. waitat 25° C. for 15 hours
4. custompartitioned with saturated sodium bicarbonate solution (500 mL)
5. washThe organic phase was washed with water (500 mL), saturated sodium chloride solution (500 mL)
6. dry with materialdried over magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. customPurification by silica gel flash chromatography (0-50% ethyl acetate in hexane)

ORD record

ord-1d12a6cfb8244f3a83a25ac2c387bb13

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365588B2