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

HRID 33409노트

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HRID 33409 반응식
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18]C)=[C:6]2[C:11]=1[NH:10][C:9](=[O:12])[NH:8][C:7]12[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.B(Br)(Br)Br>C(Cl)Cl.C(OC)(C)(C)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:18])=[C:6]2[C:11]=1[NH:10][C:9](=[O:12])[NH:8][C:7]12[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1

참가 물질

5

반응물 2

HCID 25134Boron tribromide2회HCID 693174648'-fluoro-5'-methoxy-1'H-spiro[cyclohexane-1,4'-quinazolin]-2'(3'H)-one

생성물 1

HCID 534858818'-fluoro-5'-hydroxy-1'H-spiro[cyclohexane-1,4'-quinazolin]-2'(3'H)-one수율 68%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 15413tert-Butyl methyl ether용매

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온도
5 °C

실험 절차

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%).

후처리

  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.

출처 및 근거

ORD 기록
ord-a99d2d98f9dc4202b383f8d059f99824
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07429598B2

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