Iodoethane → Ethyl 1-(5-bromopyrimidin-2-yl)-4-ethoxypiperidine-4-carboxylate

HRID 712252Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][C:11]([OH:19])([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[H-].[Na+].[CH2:22](I)[CH3:23].CCCCCC>CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:9][CH2:10][C:11]([O:19][CH2:22][CH3:23])([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12][CH2:13]2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To an ice-cold solution of ethyl 1-(5-bromopyrimidin-2-yl)-4-hydroxypiperidine-4-carboxylate (0.50 g, 1.51 mmol) in DMF (5 mL) was added NaH (0.066 g, 1.67 mmol, 60% dispersion in mineral oil) portion wiseand the mixture stirred at 0° C. for 10 minutes followed by drop wise addition of ethyl iodide (0.58 mL, 7.57 mmol). The reaction was stirred at 0° C. for 2 h. After completion of reaction (by TLC), the reaction was quenched with saturated NH4Cl solution (100 mL), extracted with EtOAc (3×100 mL) and the combined organics washed with water and brine and dried over Na2SO4. The crude residue was purified over 100-200 M silica-gel using 10% EtOAc:hexane to obtain the desired product as a yellow liquid (0.24 g, 44% yield). 1H NMR (DMSO-d6): δ 8.27 (s, 2H), 4.31 (m, 2H), 4.22 (q, J=6.40 Hz, 2H), 3.44 (m, 4H), 1.96 (m, 4H), and 1.28 (m, 6H).

Workup

stirringThe reaction was stirred at 0° C. for 2 h
customAfter completion of reaction (by TLC)
customthe reaction was quenched with saturated NH4Cl solution (100 mL)
extractionextracted with EtOAc (3×100 mL)
washthe combined organics washed with water and brine
dry with materialdried over Na2SO4
customThe crude residue was purified over 100-200 M silica-gel

Sources & evidence

ORD record: ord-ea322f0f53a14803a6c8bdfde5364be2
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181234B2

Reaction notes

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