Diisobutylaluminum hydride → (2-((4-(Difluoromethoxy)phenyl)amino)-4-methoxypyrimidin-5-yl)methanol

A solution of ethyl 2-((4-(difluoromethoxy)phenyl)amino)-4-methoxypyrimidine-5-carboxylate (0.37 g, 1.090 mmol) in THF (11 mL) was cooled to −78° C. and DIBAL-H (4.36 mL, 4.36 mmol) was added. The cold bath was removed and mixture was stirred for 1.5 h while warming to room temperature. The reaction mixture was diluted with THF (30 mL) and quenched with Na2SO4.10H2O, followed by a few drops of water. After stirring at room temperature for 18 h, the mixture was filtered through a pad of celite topped with silica gel. The pad was washed several times with methanol and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel using 30-100% ethyl acetate in hexanes. The desired fractions were concentrated to give (2-((4-(difluoromethoxy)phenyl)amino)-4-methoxypyrimidin-5-yl)methanol as an off-white solid (0.3 g, 93%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.57 (s, 1H), 8.16 (s, 1H), 7.89-7.67 (m, 2H), 7.38-6.83 (m, 3H), 4.98 (t, J=5.5 Hz, 1H), 4.36 (d, J=5.5 Hz, 2H), 3.95 (s, 3H). LCMS: R.T.=0.70; [M+H]+=298.2.

1. customThe cold bath was removed
2. additionThe reaction mixture was diluted with THF (30 mL)
3. customquenched with Na2SO4.10H2O
4. stirringAfter stirring at room temperature for 18 h
5. filtrationthe mixture was filtered through a pad of celite
6. washThe pad was washed several times with methanol
7. concentrationthe filtrate was concentrated
8. customThe residue was purified by flash chromatography on silica gel using 30-100% ethyl acetate in hexanes
9. concentrationThe desired fractions were concentrated

ORD record

ord-87188d139ded40e481c15f562a9c5c9c

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841301B2