Ethyl bromoacetate → [4-(4-Methoxybenzoyl)piperidin-1-yl]acetic acid ethyl ester
Reaction equation
[CH3:1][O: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.C(N(CC)CC)C.Br[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]>C(#N)C.C([O-])(O)=O.[Na+]>[CH2:29]([O:28][C:26](=[O:27])[CH2:25][N:14]1[CH2:15][CH2:16][CH:11]([C:9](=[O:10])[C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[CH2:12][CH2:13]1)[CH3:30]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 85 °C
Procedure
To a solution of 4-methoxy-phenyl-piperidin-4-yl-methanone (20 g, 78 mmol, 1 eq.) in 313 mL of acetonitrile was added triethylamine (22 mL, 156 mmol, 2 eq.), followed by ethyl 2-bromoacetate (9.5 mL, 86 mmol, 1.1 eq.) dropwise. The resulting mixture was heated at 85° C. overnight. After 18 h, the reaction mixture was diluted with saturated NaHCO3 (150 mL) and extracted with ethyl acetate (3×500 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give an oil. This oil was purified by silica gel column chromatography (10-20% acetone/heptane) to give the title compound as a white solid (11.7 g, 49% yield). Exact mass calculated for C17H24N1O4 306.2. MS (ESI) m/z 306.4 (M+H)+.
Workup
- extractionextracted with ethyl acetate (3×500 mL)
- washThe combined organic layers were washed with brine
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customto give an oil
- customThis oil was purified by silica gel column chromatography (10-20% acetone/heptane)
Sources & evidence
- ORD record
- ord-e47fce6a91c84bdd88c2578742a06d1e
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09181266B2
Reaction notes
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