反应详情

To a cooled (−75° C.) solution of 5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (2.0 g, 9.51 mmol) in THF (40 mL) tert.-butyllithium (15 mL, 1.5 N in pentane) is slowly added. The mixture is stirred at −78° C. for 15 min before n-propyliodide (5.22 g, 30.7 mmol) is added. Stirring is continued at −78° C. for 45 min before the reaction is quenched by adding water/methanol 1:1 (10 mL). The mixture is allowed to warm to rt, diluted with tert.-butyl methylether and 10% aq. citric acid solution. The mixture is extracted twice with EA, the combined organic extracts are washed with brine, dried over Na2SO4 and concentrated. The crude product is purified by prep. HPLC to give 5,5-dimethyl-3-propyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (200 mg) as a colourless resin; LC-MS: tR=1.04 min, [M+1]=253.31; 1H NMR (CDCl3): δ 2.98 (t, J=7.0 Hz, 2H), 2.63 (t, J=7.6 Hz, 2H), 2.36 (s br, 1H), 2.26 (s, 2H), 1.63 (hex, J=7.6 Hz, 2H), 1.51 (t, J=7.0 Hz, 2H), 0.95 (t, J=7.6 Hz, 3H), 0.94 (s, 6H).

1. additionis slowly added
2. additionis added
3. customis quenched
4. additionby adding water/methanol 1:1 (10 mL)
5. additiondiluted with tert.-butyl methylether and 10% aq. citric acid solution
6. extractionThe mixture is extracted twice with EA
7. washthe combined organic extracts are washed with brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated
10. customThe crude product is purified by prep