[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][C:7]2[C:11]([C:12]#[N:13])=[C:10]([C:14]3[CH2:15][CH2:16][O:17][CH2:18][CH:19]=3)[S:9][C:8]=2[C:20]([O:22]CC)=[O:21])=[CH:4][CH:3]=1.O1CCCC1.[OH-].[Na+].CO>>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][C:7]2[C:11]([C:12]#[N:13])=[C:10]([C:14]3[CH2:15][CH2:16][O:17][CH2:18][CH:19]=3)[S:9][C:8]=2[C:20]([OH:22])=[O:21])=[CH:4][CH:3]=1To a round bottom flask containing ethyl 3-(4-chlorobenzyl)-4-cyano-5-(3,6-dihydro-2H-pyran-4-yl)thiophene-2-carboxylate (43.0 mg, 0.111 mmol) were added tetrahydrofuran (1.23 mL, 15.2 mmol), sodium hydroxide (1.0N in water, 0.925 mL, 0.925 mmol), and methanol (0.617 mL, 15.2 mmol). The mixture was stirred at room temperature overnight. Reaction was quenched via addition of 1N HCl in water (2 mL), then diluted with EtOAc and transferred to separatory funnel. The layers were separated, and the aqueous layer was extracted 2× with EtOAc. Combined organics were washed with brine, dried over Na2SO4, and filtered, at adsorbed to Celite (10 mL). Column chromatography (40 g ISCO column, gradient elution 0-8% MeOH/DCM afforded 3-(4-chlorobenzyl)-4-cyano-5-(3,6-dihydro-2H-pyran-4-yl)thiophene-2-carboxylic acid (95) (25 mg, 63%) as a white solid. LC/MS: (FA) ES− 358, 360; 1H NMR (400 MHz, DMSO) δ 14.04 (br s, 1H), 7.33 (d, J=8.5, 2H), 7.26 (d, J=8.5, 2H), 6.64 (s, 1H), 4.43 (s, 2H), 4.24 (d, J=2.9, 2H), 3.79 (dd, J=5.4, 5.4, 2H), 3.32 (br s, 2H).
Loading…
