Sodium Hydroxide → Tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetic acid

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Reaction Conditions

Reaction Steps

To a solution of Methyl tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetate (Preparation 10, 63.95 g, 135 mmol) in tetrahydrofuran (1 L) and methylated spirit (1 L) was dropwise added aqueous sodium hydroxide (1 M, 811 mL, 811 mmol). The resulting mixture was stirred at 60° C. for 90 minutes and then allowed to cool to room temperature overnight. The volatile solvents were removed in vacuo, and the remaining aqueous residue was diluted with water (400 mL) and extracted with tert-butyl methyl ether (600 mL). The organic layer was washed with water (400 mL) and then cooled on ice. 2 M hydrochloric acid was added to pH 5 and the resulting solids were collected by filtration, washing with water. The solid was dissolved in 2-methyl tetrahydrofuran (300 mL) and stirred for 10 minutes. An aqueous layer had appeared and this was separated. The aqueous layer was extracted with 2-methyl tetrahydrofuran (2×300 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to give the title compound as a pale yellow solid, 54.35 g, in an 88% yield. 1H NMR (400 MHz, CDCl3) δ ppm 1.27 (s, 9H), 1.81-1.93 (m, 4H), 2.65 (s, 3H), 2.76-2.88 (m, 2H), 3.20-3.27 (m, 2H), 6.13 (s, 1H), 9.66 (br s, 1H).

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