Ethyl bromoacetate → [4-(2-Trifluoromethoxy-benzoyl)-piperidin-1-yl]-acetic acid ethyl ester
Reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][C:16]([F:19])([F:18])[F:17])=[O:8])[CH2:3][CH2:2]1.CCN(CC)CC.Br[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30]>C(#N)C>[CH2:32]([O:31][C:29](=[O:30])[CH2:28][N:1]1[CH2:6][CH2:5][CH:4]([C:7](=[O:8])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][C:16]([F:17])([F:18])[F:19])[CH2:3][CH2:2]1)[CH3:33]Participants
5
Conditions
- Temperature
- 85 °C
Procedure
To a solution of piperidin-4-yl-(2-trifluoromethoxy-phenyl)-methanone in 5 mL of acetonitrile was added Et3N (0.3 mL, 2.4 mmol, 2 eq.), followed by ethyl 2-bromoacetate (0.14 mL, 1.3 mmol, 1.1 eq.) added dropwise and heated at 85° C. overnight. After 18 h, the reaction mixture was concentrated in vacuo, diluted with saturated NaHCO3 (100 mL) and extracted with ethyl acetate (3×50 mL). The combine organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to give a dark oil. This oil was purified by silica gel column chromatography (30-50% ethyl acetate/heptane) to give the title as a light brown oil (0.36 g, 85%). Exact mass calculated for C18H22F3N1O4 360.1. MS (ESI) m/z 360.7 (M+H)+.
Workup
- additionadded dropwise
- concentrationthe reaction mixture was concentrated in vacuo
- additiondiluted with saturated NaHCO3 (100 mL)
- extractionextracted with ethyl acetate (3×50 mL)
- washThe combine organic layers were washed with brine
- dry with materialdried over anhydrous Na2SO4
- concentrationconcentrated in vacuo
- customto give a dark oil
- customThis oil was purified by silica gel column chromatography (30-50% ethyl acetate/heptane)
Sources & evidence
- ORD record
- ord-8d4e823a316442a78a2696339e71e68f
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09181266B2
Reaction notes
Loading…