Potassium Carbonate → 3-(1-hydroxy-ethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester

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Reaction Steps

Add sodium hydride (60% in mineral oil, 2.12 g, 0.053 mol) to a solution of mercapto-acetic acid methyl ester (2.8 g, 0.026 mol) in tetrahydrofuran (100 mL) at −10° C.˜0° C. and stirred the mixture at −10° C.˜0° C. for 1 hour. Then add a mixture of 1-chloro-1-(2-oxocyclopentylidene)propan-2-yl acetate and 1-(2-chlorocyclopent-1-enyl)-1-oxopropan-2-yl acetate (5.47 g, 0.025 mol, 6:1) in tetrahydrofuran (15 mL) at 0° C. After stirring at 0° C. for overnight, dilute the reaction mixture with water and extract with ethyl acetate. The combined organic layers are washed with brine, dried over anhydrous Na2SO4 and concentrated. The residue and K2CO3 (6.9 g, 0.05 mol) in MeOH (20 mL) is heated at 50° C. overnight. The solvent is removed. The residue is purified by silica gel chromatograph (eluting with 2.5% to 10% ethyl acetate in petroleum ether) to give 3-(1-hydroxy-ethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester (3.2 g, 14.1 mmol, 35.6% for 2 steps) as yellow oil. 1H NMR (CDCl3, 400 MHz): δ 5.03 (m, 1H), 3.83 (m, 3H), 2.88 (m, 2H), 2.66 (m, 2H), 2.38 (m, 2H), 2.12 (s, 1H), 1.54 (d, J=7.2, 3H).

Provenance & Evidence