反应详情

A mixture of 1.73 g (5.50 mmol) of (6aR-trans)-6a,7,8,10a-Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol, 10 ml of dimethylsulfoxide, 3 ml of ethyl 4-bromobutyrate and 1.73 g of potassium carbonate was degassed and then heated under reflux under argon over night. The reaction was cooled, diluted with 250 ml of water and extracted with ether. The extracts were passed over a column of silica gel, and the fractions containing the intermediate ester were combined and concentrated under vacuum. The residue was dissolved in 100 ml of methanol, the solution was heated to boiling and 20 ml of water, followed by 2.2 g of sodium carbonate, was added. The mixture was heated under reflux for 3 hrs. The methanol was evaporated under vacuum, and the aqueous residue was acidified with hydrochloric acid and extracted with dichloromethane. The extracts were concentrated, and the residue was dissolved in hexane and adsorbed onto silica gel. Elution with 15% ethyl acetate in benzene, followed by evaporation, gave 1.70 g (77%) of (6aR-trans)-4-[(6a,7,8,10a-Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-yl)oxy]butanoic acid as a colorless oil: ir (CHCl3) 1710 cm-1 ; uv max (C2H5OH) 225 nm (infl) (ε17,830), 274 (1090), and 282 (1120); nmr (CDCl3) δ11.3 (br, CO2H), 6.29 and 6.20 (two sharp d, H-2 and H-4), 5.41 (m, H-8), 4.01 (t, OCH2C), 3.18 (m, H-10a), 2.59 (t, ArCH2C), 2.48 (t, CCH2CO), 1.69 (s, 9-CH3), 1.34 and 1.06 (two s, 6,6-diCH3), and 0.87 (t, ω-CH3); mass mol wt 400; [α]D25° -195.3° (c 1.104, CHCl3).

1. customwas degassed
2. temperatureheated
3. temperatureunder reflux under argon over night
4. temperatureThe reaction was cooled
5. additiondiluted with 250 ml of water
6. extractionextracted with ether
7. additionthe fractions containing the intermediate ester
8. concentrationconcentrated under vacuum
9. dissolutionThe residue was dissolved in 100 ml of methanol
10. temperaturethe solution was heated
11. additionwas added
12. temperatureThe mixture was heated
13. temperatureunder reflux for 3 hrs
14. customThe methanol was evaporated under vacuum
15. extractionextracted with dichloromethane
16. concentrationThe extracts were concentrated
17. dissolutionthe residue was dissolved in hexane
18. washElution with 15% ethyl acetate in benzene
19. customfollowed by evaporation