Benzaldehyde → 3-Bromo-5-(hydroxy-phenyl-methyl)-pyridin-4-one

To a heterogeneous mixture of 3,5-dibromo-pyridin-4-one 10 (0.313 g, 1.24 mmol) in anhydrous THF (4 mL) at −78° C. under nitrogen atmosphere was added phenylmagnesium bromide solution (1.36 mL of 1 M solution in THF, 1.36 mmol) [Borzilleri, et al., U.S. Pat. 20050245530]. After stirring for 15 min, n-BuLi solution (0.68 mL of 2 M solution in cyclohexane, 1.36 mmol) was added and the reaction mixture stirred for 15 min at −78° C. under nitrogen atmosphere. To this mixture was added benzaldehyde (0.26 mL, 2.6 mmol) and the mixture was stirred for 2 h at −78° C. The reaction mixture was quenched by adding HOAc (0.38 mL) and TFA (0.38 mL), concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (dichloromethane:methanol, 95:5). Yield 0.125 g (36%), white solid, 123-124° C. 1H NMR (MeOH— d4, 500 MHz): δ 8.09 (s, 1H), 7.81 (s, 1H), 7.38-7.17 (m, 5H), 5.92 (s, 1H), 3.83 (s, 2H). 13C NMR (MeOH— d4, 125 MHz): δ 174.3, 144.4, 139.7, 135.8, 133.6, 129.4, 129.3, 128.6, 128.0, 128.0, 114.8, 70.8.

1. stirringthe reaction mixture stirred for 15 min at −78° C. under nitrogen atmosphere
2. stirringthe mixture was stirred for 2 h at −78° C
3. customThe reaction mixture was quenched
4. additionby adding HOAc (0.38 mL) and TFA (0.38 mL)
5. concentrationconcentrated in vacuo
6. customthe residue was purified by flash column chromatography on silica gel (dichloromethane:methanol, 95:5)
7. customYield 0.125 g (36%), white solid, 123-124° C

ORD record

ord-fc9ab1b907b04eeb95c41807507499de

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07888375B2