4-Hydroxybenzaldehyde → 4-([1,3]Thiazolo[4,5-b]pyridin-2-yloxy)benzaldehyde

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Reaction Conditions

Reaction Steps

To a 1-L, round-bottom, 3-necked flask equipped with overhead mechanical stirring, dynamic nitrogen inlet, and thermocouple probe were added 2-chloro-thiazolo[4,5-b]pyridine (51.41 g, 0.248 mol), K2CO3 (38.0 g, 0.275 mol), and CH3CN (400 mL). The resultant slurry was aged at rt for 1 h. The 4-hydroxy-benzaldehyde (30.4 g, 0.248 mol) was then added to the reaction mixture followed by K2CO3 (38.0 g, 0.275 mol). The resultant slurry was diluted with additional CH3CN (100 mL), heated to reflux, and aged for 3.5 h. The solution was cooled to 50° C. and filtered. The inorganic cake was washed with CH3CN (2×100 mL). The washes were added to the filtrate. The filtrate was concentrated until nucleation was observed (removal of ˜350 mL of CH3CN was required). The resultant slurry was heated to reflux and slowly cooled to rt during an overnight aging. The resultant slurry was cooled to 2° C. and filtered. The cake was transferred to a vacuum oven and dried at 55° C. for 16 h to yield 4-(thiazolo[4,5-b]pyridin-2-yloxy)-benzaldehyde (51.6 grams, 0.201 mol) as an orange/red powder. The mother liquor was concentrated and an additional crop of 4-(thiazolo[4,5-b]pyridin-2-yloxy)-benzaldehyde (6.2 g, 0.024 mol) was obtained from recrystallization from CH3CN. 1H NMR (400 MHz, CDCl3): 10.03 (s, 1H), 8.60 (dd, J=4.8, 1.6 Hz, 1H), 8.09 (dd, J=8.0, 1.6 Hz, 1H), 8.03-7.96 (m, 2H), 7.73-7.65 (m, 2H), 7.32-7.22 (m, 1H). MS (ESI): mass calcd. for C13H8N2O2S, 256.03; m/z found, 257.0[M+H]+.

Provenance & Evidence