Boron tribromide → 8'-fluoro-5'-hydroxy-1'H-spiro[cyclohexane-1,4'-quinazolin]-2'(3'H)-one

Temperature

5 °C

To a stirred solution of 8′-fluoro-5′-methoxy-1′H-spiro[cyclohexane-1,4′-quinazolin]-2′(3′H)-one (2.34 g, 8.84 mmol) in DCM (250 mL) at 0 to 5° C. was added boron tribromide (11.07 g, 44.2 mmol) dropwise over 20 minutes under N2. The mixture was stirred at 5° C. for 10 mins and gradually allowed to warm up to ambient temperature. Stirring was continued at ambient temperature for 18 h and a further portion of BBr3 (5 g, 20 mmol) was added. The mixture was left to stir for a further 24 hours and quenched with saturated NaHCO3 solution (500 mL) at 10° C. over 30 minutes. The mixture was stirred at ambient temperature for 1 hour and the aqueous layer was separated from dichloromethane and extracted with ethyl acetate (2×500 mL). The organic layers were washed with saturated NaHCO3 solution (200 mL), water (300 mL), dried over anhydrous MgSO4, filtered and concentrated in vacuo at 40° C. to give the crude product. The crude material was slurred in tert-butylmethylether (10 mL) at 18 to 20° C. for 5 minutes, filtered and dried in vacuo at 40° C. to give 8′-fluoro-5′-hydroxy-1′H-spiro[cyclohexane-1,4′-quinazolin]-2′(3′H)-one (1.5 g, 68%) as a light-brown solid, purity (99.9%).

1. temperatureto warm up to ambient temperature
2. stirringStirring
3. waitwas continued at ambient temperature for 18 h
4. waitThe mixture was left
5. stirringto stir for a further 24 hours
6. customquenched with saturated NaHCO3 solution (500 mL) at 10° C. over 30 minutes
7. stirringThe mixture was stirred at ambient temperature for 1 hour
8. customthe aqueous layer was separated from dichloromethane
9. extractionextracted with ethyl acetate (2×500 mL)
10. washThe organic layers were washed with saturated NaHCO3 solution (200 mL), water (300 mL)
11. dry with materialdried over anhydrous MgSO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo at 40° C.
14. customto give the crude product
15. filtrationfiltered
16. customdried in vacuo at 40° C.

ORD record

ord-a99d2d98f9dc4202b383f8d059f99824

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07429598B2