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

HRID 712251Notes

Reaction equation

[OH:1][C:2]1([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.[Br:22][C:23]1[CH:24]=[N:25][C:26](Cl)=[N:27][CH:28]=1.O>CCO>[Br:22][C:23]1[CH:24]=[N:25][C:26]([N:5]2[CH2:4][CH2:3][C:2]([OH:1])([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:7][CH2:6]2)=[N:27][CH:28]=1

Participants

Conditions

Temperature: 80 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-c2f19afd2a434dbaac033258eb3efcdd
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181234B2

Reaction notes

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