反应详情

Heat a suspension of NaH (60% suspension in mineral oil, 49 mg, 1.2 mmol) in DMSO (6 mL) to 80° C. under N2 until evolution of H2 stops. Dissolve (3-nitro-benzyl)-phosphonic acid diethyl ester (prepared according to procedures as described in Okamoto et. al., Bull. Chem. Soc. Jpn. (1987), 60(1), 277-82) (338 mg, 1.2 mmol) in DMSO (1 mL) and add to reaction mixture. Add 1-chloro-10,11-dihydro-dibenzo[a,d]cyclohepten-5-one (prepared according to procedures as described in Humber et al., J. Med. Chem. (1978), 21(12), 1225-31) (200 mg, 0.824 mmol) at once and heat to 100° C. for 48 h. Cool to room temperature. Dilute reaction mixture with ethyl acetate (50 mL) and wash twice with H2O. Dry (MgSO4) and concentrate organics to a brown oil. Chromatograph on silica gel (10 g), eluting with 2% to 4% ethyl acetate/hexanes to afford a mixture of compounds. Dissolve this mixture in ethanol (10 mL) and add SnCl2 (dihydrate, 508 mg, 2.25 mmol). Heat to reflux for 3 h and cool to room temperature. Concentrate reaction mixture, then dissolve residue in diethyl ether. Wash organics with H2O, 1.00N aqueous NaOH, then twice with H2O. Dry (MgSO4) and concentrate organics to a yellow oil. Chromatograph on silica gel (10 g), eluting with 5% to 10% ethyl acetate/hexanes to afford 28 mg (10%) of the title compound as a colorless oil. MS (ES) 330 (M+H); HPLC reveals 36:64 mixture of geometric isomers—36% at 4.977 min, 64% at 5.218 min—overall 100% purity.

1. temperatureHeat
2. additionDilute
3. washwash twice with H2O
4. dry with materialDry (MgSO4)
5. concentrationconcentrate organics to a brown oil
6. washChromatograph on silica gel (10 g), eluting with 2% to 4% ethyl acetate/hexanes
7. customto afford
8. additiona mixture of compounds
9. temperatureHeat
10. temperatureto reflux for 3 h
11. temperaturecool to room temperature
12. concentrationConcentrate
13. customreaction mixture
14. dry with materialDry (MgSO4)
15. concentrationconcentrate organics to a yellow oil
16. washChromatograph on silica gel (10 g), eluting with 5% to 10% ethyl acetate/hexanes