Water → Ethyl 1-(5-bromopyrimidin-2-yl)-4-hydroxypiperidine-4-carboxylate

Temperatur

80 °C

To an ice-cold solution of ethyl 4-hydroxypiperidine-4-carboxylate (0.60 g, 3.44 mmol) in EtOH (15 mL) was added DIPEA (2.95 mL, 17.24 mmol) followed by the addition of 5-bromo-2-chloropyrimidine (0.67 g, 3.44 mmol). The reaction was heated to 80° C. for 3 h then cooled to rt, water added and extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 20% EtOAc:hexane to obtain the desired product as a yellow solid (0.57 g, 88%). 1H NMR (DMSO-d6): δ 8.44 (s, 2H), 5.58 (s, 1H), 4.27 (m, 2H), 4.10 (q, J=7.20 Hz, 2H), 3.28 (m, 2H), 1.81 (m, 2H), 1.66 (m, 2H), and 1.18 (t, J=7.20 Hz, 3H).

1. temperaturethen cooled to rt
2. extractionextracted with EtOAc (3×100 mL)
3. washThe combined organics were washed with brine
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. customevaporated under reduced pressure
7. customThe crude residue was purified over 100-200 M silica-gel

ORD-Eintrag

ord-c2f19afd2a434dbaac033258eb3efcdd

Quelldatensatz

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09181234B2