Sodium Hydroxide → 3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)propanoic acid

Participants

Reaction Conditions

Reaction Steps

2-Methyltetrahydrofuran (142.1 mL) was added to Pd-118 (4.52 g) to give a red solution. To this solution was added a solution of sodium hydroxide (41.6 g) in water (473.5 mL), followed by a solution of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (81.81 g) in 2-methyltetrahydrofuran (142.1 mL), followed by the solution of 3-(3-bromophenethoxy)propanoic acid (94.7 g, prepared as in Preparation 3, Step (ii)) in 2-methyltetrahydrofuran (585 mL solution volume). The mixture was then heated to reflux and at reflux for 30 min then allowed to cool to 20° C. The mixture was filtered through GF/F filter paper then the layers separated. 20% w/w Citric acid (568.2 mL) was added to the separated aqueous layer, followed by 2-methyltetrahydrofuran (568.2 mL). After mixing, the layers were separated, the organic layer diluted with 2-methyltetrahydrofuran (to make the solution up to 950 mL) and filtered to give a small sample of the subtitled compound as an off-white solid (5.63 g). 800 mL of the filtrate (total volume 930 mL) was passed through a cartridge filter containing charcoal. The solution was partially evaporated under vacuum to give a solution measuring 490 mL and split into 2 portions. Firstly half of the solution was cooled to 20° C. and added to dibutyl ether (400 mL) at 20° C. to give a precipitate which was stirred at 20° C. for 2 h. The suspension was filtered, washed with dibutyl ether (100 mL) and dried at 50° C. under vacuum to afford the sub-titled compound (34.1 g). The second half of the solution was added to dibutyl ether (400 mL) at 65° C. to give a precipitate which was maintained at 65° C. for 10 min then cooled to 15° C. and stirred for 1 h. The suspension was filtered, washed with dibutyl ether (100 mL) and dried at 50° C. under vacuum to afford the subtitled compound as a white solid (30.5 g). MS [M+H]+=275.2 (MultiMode+) 1H NMR (400 MHz, DMSO-d6) δ 12.15 (s, 1H), 8.09 (s, 1H), 7.83 (s, 1H), 7.43 (s 1H), 7.37 (d, 1H), 7.24 (t, 1H), 7.05 (d, 1H), 3.86 (s, 3H), 3.62 (t, 2H), 3.61 (t, 2H), 2.80 (t, 2H), 2.45 (t, 2H).

Provenance & Evidence