4-(Difluoromethoxy)aniline → Ethyl 2-((4-(difluoromethoxy)phenyl)amino)-4-methoxypyrimidine-5-carboxylate

HRID 77463Notes

Reaction equation

[F:1][CH:2]([F:11])[O:3][C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[CH:6][CH:5]=1.[CH3:12][O:13][C:14]1[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][N:17]=[C:16](S(C)(=O)=O)[N:15]=1>O1CCOCC1>[F:1][CH:2]([F:11])[O:3][C:4]1[CH:10]=[CH:9][C:7]([NH:8][C:16]2[N:15]=[C:14]([O:13][CH3:12])[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][N:17]=2)=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 4-(difluoromethoxy)aniline (0.285 mL, 2.305 mmol) and ethyl 4-methoxy-2-(methylsulfonyl)pyrimidine-5-carboxylate (0.4 g, 1.537 mmol) in dioxane was heated in the microwave at 150° C. for 50 min. The mixture was then cooled to room temperature and concentrated. The residue was purified by flash chromatography on silica gel using 5-50% ethyl acetate in hexanes. The desired fractions were concentrated to give ethyl 2-((4-(difluoromethoxy)phenyl)amino)-4-methoxypyrimidine-5-carboxylate as an orange solid (0.37 g, 71%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.83 (s, 1H), 7.67-7.58 (m, 2H), 7.37 (br. s., 1H), 7.20-7.09 (m, 2H), 6.74-6.12 (m, 1H), 4.35 (q, J=7.0 Hz, 2H), 4.08 (s, 3H), 1.38 (t, J=7.0 Hz, 3H). LCMS: R.T.=0.96; [M+H]+=340.1.

Workup

temperatureThe mixture was then cooled to room temperature
concentrationconcentrated
customThe residue was purified by flash chromatography on silica gel using 5-50% ethyl acetate in hexanes
concentrationThe desired fractions were concentrated

Sources & evidence

ORD record: ord-f0d8b80bc0ef44d2a410809e25d7db3e
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841301B2

Reaction notes

Loading…