反应详情

温度

5 °C

To a solution of 3-methyl-3-sulfanylbutanoic acid (Sweetman et al, J. Med Chem.,14:868 (1971), the disclosure of which is incorporated herein by reference in its entirety) (4.6 g, 34 mmol) in methylene chloride (250 mL) under nitrogen and cooled over ice/salt to 5° C. (internal temperature) was added trifluoroacetic acid (82 g, 0.72 mol). No significant temperature rise was noted during the addition. To this was then added dropwise a solution of 2,4,6-trimethoxybenzyl alcohol (Munson et al., J. Org. Chem., 57, 3013 (1992), the disclosure of which is incorporated herein by reference in its entirety) (6.45 g, 32 mmol) in methylene chloride (150 mL) such that the reaction temperature does not rise above 5° C. After the addition was complete, the mixture was stirred for an additional 5 minutes at 5° C. and the volatiles were evaporated in vacuo (toluene or ethyl acetate can be used to assist in the removal of volatile material). The residue was partitioned between diethyl ether and water and the organic phase dried over anhydrous sodium sulfate, filtered and the volatile material evaporated in vacuo. The residue was treated with activated charcoal and recrystalized from diethyl ether/hexane. The product was isolated as a white solid in 70% yield (7 g). mp 103-105° C.; 1H NMR(CDCl3): δ6.12 (s, 2H), 3.80-3.85 (m, 11H), 2.74 (s, 2H), 1.47 (s, 6H). 13C NMR (CDCl3): δ173.9, 160.6, 158.6, 105.6, 90.5, 55.7, 55.3, 45.9, 43.6, 28.4, 21.0.

1. additionNo significant temperature rise was noted during the addition
2. customdoes not rise above 5° C
3. additionAfter the addition
4. customthe volatiles were evaporated in vacuo (toluene or ethyl acetate
5. customto assist in the removal of volatile material)
6. customThe residue was partitioned between diethyl ether and water
7. dry with materialthe organic phase dried over anhydrous sodium sulfate
8. filtrationfiltered
9. customthe volatile material evaporated in vacuo
10. additionThe residue was treated with activated charcoal
11. customrecrystalized from diethyl ether/hexane
12. customThe product was isolated as a white solid in 70% yield (7 g)