Hydrochloric Acid → [(1S)-5-({3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenoxy]propyl}sulfanyl)-2,3-dihydro-1H-inden-1-yl]acetic acid

Participants

Reaction Steps

To a solution of ethyl [(1S)-5-({3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenoxy]propyl}sulfanyl)-2,3-dihydro-1H-inden-1-yl]acetate (50 mg, 0.09 mmol) (Example 509) in a mixture of THF (2 mL), ethanol (1 mL), and water (2 mL) was added LiOH (8.7 mg, 0.36 mmol). The reaction mixture was stirred vigorously at rt for 18 h, and then it was acidified to pH ˜2 using HCl (1M aqueous solution). The aqueous phase was extracted with CH2Cl2, and the combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (4:1 hexanes/EtOAc) to give the title compound (18 mg, 38%) as a white solid. 1H NMR (400 MHz, CDCl3) 7.64 (d, 1H), 7.62 (dd, 1H), 7.22 (s, 1H), 7.15 (d, 1H), 7.08 (d, 1H), 6.75 (d, 1H), 4.31 (t, 2H), 4.15-4.05 (m, 2H), 3.58-3.50 (m, 1H), 3.12 (t, 2H), 2.93-2.80 (m, 2H), 2.78 (t, 2H), 2.78-2.73 (m, 1H), 2.60 (t, 2H), 2.49 (dd, 1H), 2.45-2.36 (m, 1H), 2.17-2.06 (m, 4H), 1.81-1.73 (m, 1H), 1.68-1.58 (m, 2H), 0.95 (t, 3H); LC-MS: RT=4.54 min, (M+H)+ 524.2.

Provenance & Evidence