Acetic Acid → 9a-butyl-8-chloro-6-fluoro-7-methoxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one

HRID 7898

반응식

HRID 7898 반응식
C(C1CC2C(=CC(F)=C(OC)C=2Cl)C1=O)CCC.C(C(C)=O)=C.C[O-].[Na+].CO.[CH2:29]([C:33]1([CH2:47][CH2:48][C:49](=[O:51])[CH3:50])[CH2:41][C:40]2[C:35](=[CH:36][C:37]([F:45])=[C:38]([O:43][CH3:44])[C:39]=2[Cl:42])[C:34]1=O)[CH2:30][CH2:31][CH3:32].N1CCCC1.C(O)(=O)C>O1CCCC1.C1(C)C=CC=CC=1>[CH2:29]([C:33]12[CH2:47][CH2:48][C:49](=[O:51])[CH:50]=[C:34]1[C:35]1[C:40](=[C:39]([Cl:42])[C:38]([O:43][CH3:44])=[C:37]([F:45])[CH:36]=1)[CH2:41]2)[CH2:30][CH2:31][CH3:32]

참가 물질

10

반응물 7

HCID 176Acetic AcidHCID 887MethanolHCID 6570Methyl vinyl ketoneHCID 31268PyrrolidineHCID 10942334Sodium MethoxideHCID 219908612-Butyl-4-chloro-6-fluoro-5-methoxy-1-indanoneHCID 219908642-Butyl-4-chloro-6-fluoro-5-methoxy-2-(3-oxobutyl)-1-indanone

생성물 1

HCID 219909369a-butyl-8-chloro-6-fluoro-7-methoxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of crude 2-butyl-4-chloro-6-fluoro-5-methoxy-1-indanone (386 mg, 1.4 mmol) in tetrahydrofuran (2.8 mL) was treated with methyl vinyl ketone (0.150 mL, 1.78 mmol) and 0.5N sodium methoxide in methanol (1.1 mL, 0.56 mmol). The mixture was stirred at room temperature for 5.5 hours to effect conversion to 2-butyl-4-chloro-6-fluoro-5-methoxy-2-(3-oxobutyl)-1-indanone. The reaction mixture was diluted with toluene (10 mL), treated with pyrrolidine (0.117 mL, 1.4 mmol) and acetic acid (0.112 mmol, 1.46 mmol), and then stirred and heated in an oil bath at 80° C. for 3 hours. After storing overnight at room temperature, the mixture was partitioned between EtOAc (50 mL) and water (50 mL). The organic phase was washed with 0.1N HCl (50 mL), saturated aqueous NaHCO3 (50 mL) and brine (20 mL), dried over MgSO4, filtered, and evaporated under vacuum. The oily residue was purified by preparative layer chromatography on four 0.1×20×20 cm silica gel GF plates, developing with 5% EtOAc in CH2Cl2. The product bands were combined, eluted with EtOAc, and the eluent evaporated under vacuum to provide 9a-butyl-8-chloro-6-fluoro-7-methoxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one (160 mg) as a solid. 1H NMR spectroscopy revealed that the product contained a minor amount of the isomeric product 9a-butyl-6-chloro-8-fluoro-7-methoxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one which is derived from a minor amount of 2-butyl-6-chloro-4-fluoro-5-methoxy-1-indanone in the starting material.

후처리

  1. stirringstirred
  2. temperatureheated in an oil bath at 80° C. for 3 hours
  3. waitAfter storing overnight at room temperature
  4. customthe mixture was partitioned between EtOAc (50 mL) and water (50 mL)
  5. washThe organic phase was washed with 0.1N HCl (50 mL), saturated aqueous NaHCO3 (50 mL) and brine (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated under vacuum
  9. customThe oily residue was purified by preparative layer chromatography on four 0.1×20×20 cm silica gel GF plates
  10. washeluted with EtOAc
  11. customthe eluent evaporated under vacuum

출처 및 근거

ORD 기록
ord-f4004a05731743db9d750d86b5473e91
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07087599B2

연결된 노트

불러오는 중…