Boron tribromide → 5-[3-(4-Hydroxyphenoxy)azetidin-1-yl]-5-methyl-2,2-diphenylhexanamide

Temperature

0 °C

The product of example 106(53 mg, 0.16 mmol) was dissolved in dichloromethane (5 mL) and the solution was cooled to 0° C. Boron tribromide (1M in dichloromethane, 0.52 mL, 0.52 mmol) was added and the solution was stirred at 0° C. for 35 minutes. Further boron tribromide (1M in dichloromethane, 0.52 mL, 0.52 mmol) was added and stirring continued at 0° C. for 30 minutes. The reaction was then quenched with saturated sodium hydrogen carbonate solution (20 mL) and stirred at room temperature for 18 hours. The aqueous layer was separated, extracted with ethyl acetate (25 mL) and the combined organic solution was dried over magnesium sulfate and concentrated in vacuo to give a gum. The gum was re-dissolved in dichloromethane (5 mL) and the solution was cooled to −10° C. Boron tribromide (1M in dichloromethane, 0.52 mL, 0.52 mmol) was added and the mixture was stirred at −10° C. for 1 hour. The reaction was then quenched with saturated sodium hydrogen carbonate solution (20 mL) and the organic layer was separated and extracted with ethyl acetate (20 mL). The combined organic solution was dried over magnesium sulfate, concentrated in vacuo and the residue was purified by column chromatography on silica gel, eluting with pentane:ethyl acetate/methanol/0.88 ammonia (90/10/1), 75:25 to 50:50, to afford the title compound as a colourless foam in 27% yield (14 mg).

1. stirringstirring
2. waitcontinued at 0° C. for 30 minutes
3. customThe reaction was then quenched with saturated sodium hydrogen carbonate solution (20 mL)
4. stirringstirred at room temperature for 18 hours
5. customThe aqueous layer was separated
6. extractionextracted with ethyl acetate (25 mL)
7. dry with materialthe combined organic solution was dried over magnesium sulfate
8. concentrationconcentrated in vacuo
9. customto give a gum
10. temperaturethe solution was cooled to −10° C
11. stirringthe mixture was stirred at −10° C. for 1 hour
12. customThe reaction was then quenched with saturated sodium hydrogen carbonate solution (20 mL)
13. customthe organic layer was separated
14. extractionextracted with ethyl acetate (20 mL)
15. dry with materialThe combined organic solution was dried over magnesium sulfate
16. concentrationconcentrated in vacuo
17. customthe residue was purified by column chromatography on silica gel
18. washeluting with pentane

ORD record

ord-f50c615c1d7942fc9e08f866b6bb2348

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486992B2