Ammonia → HCID 17862916, compound

Temperature

-78 °C

2-Chloro-4-methyl-nicotinic acid methyl ester (1 g. 5.4 mmol) was dissolved in THF (10 mL) and cooled to −78° C. and DIBAL (1 M in toluene) was added via a syringe (14.4 mL. 21.6 mmol). The reaction mixture was allowed to warm to RT over a period of 4 h. Additional DIBAL (5 mL. 5 mmol) was added and the reaction was stirred at RT for 1 h before cooled to −20° C. Water (2 mL). sat. Na2CO3 solution (1.5 mL). aqueous NH3 (3 mL) and ACN (70 mL) were added. After vigorous stirring for 30 min. the suspension was centrifuged and the precipitate suspended in a solution of ACN (100 mL) and concentrated aqueous NH3 (5 mL). After vigorous stirring for 30 min the suspension was centrifuged. The combined supernatants were concentrated in vacuo to yield crude (2-chloro-4-methyl-pyridin-3-yl)-methanol which was converted into the title compound according to the procedure described for the preparation of 3-bromo-5-chloro-4-(tetrahydro-pyran-2-yloxymethyl)-pyridine. MS (m/z): 158.0 [M+H+].

1. temperatureto warm to RT over a period of 4 h
2. temperaturebefore cooled to −20° C
3. stirringAfter vigorous stirring for 30 min. the suspension
4. stirringAfter vigorous stirring for 30 min the suspension
5. concentrationThe combined supernatants were concentrated in vacuo

ORD record

ord-ee2317e015114074bfc21da4e03100f9

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410134B2