Ethyl bromoacetate → Ethyl 2-(4-(4-fluorobenzoyl)piperidin-1-yl)acetate

HRID 713424Notes

Reaction equation

HRID 713424 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[O:10])=[CH:5][CH:4]=1.Br[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].C(N(CC)CC)C>C(#N)C>[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH:11]2[CH2:16][CH2:15][N:14]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:13][CH2:12]2)=[O:10])=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 8471TriethylamineHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochloride

Product 1

HCID 71227338Ethyl 2-(4-(4-fluorobenzoyl)piperidin-1-yl)acetateYield 85%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (4-fluorophenyl)(piperidin-4-yl)methanone hydrochloride (51.8 g, 213 mmol) in acetonitrile (400 mL) was added ethyl 2-bromoacetate (38.2 mL, 345 mmol) and triethylamine (70 mL, 506 mmol). The mixture was heated at reflux for 5 h, the solvent was evaporated under reduced pressure and purified via flash column chromatography (ethyl acetate:hexane, 10:90 to 100:0) to provide product (52.7 g, 85% yield). 1H NMR (400 MHz, CDC3) δ 7.98 (dd, J=8.5, 5.5 Hz, 2H), 7.16 (t, J=8.5 Hz, 2H), 4.22 (q, J=7.2 Hz, 2H), 3.16-3.27 (m, 1H), 3.03 (d, J=11.5 Hz, 2H), 2.43 (td, J=11.2, 3.3 Hz, 2H), 1.81-2.09 (m, 4H), 1.51-1.73 (m, 2H), 1.30 (t, J=7.3 Hz, 3H). MS m/z 294.4 (M+1), retention time=1.94 min.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 5 h
  3. customthe solvent was evaporated under reduced pressure
  4. custompurified via flash column chromatography (ethyl acetate:hexane, 10:90 to 100:0)

Sources & evidence

ORD record
ord-6b22ce69d3fd47e296c373e01ad4d062
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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