Water → 4-[2-(4-Fluorophenyl)ethylidene]-piperidine-1-carboxylic acid benzyl ester
Reaction equation
[Br-].[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:5][CH:4]=1.O=[C:31]1[CH2:36][CH2:35][N:34]([C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:38])[CH2:33][CH2:32]1.O>C1COCC1>[CH2:40]([O:39][C:37]([N:34]1[CH2:35][CH2:36][C:31](=[CH:10][CH2:9][C:6]2[CH:5]=[CH:4][C:3]([F:2])=[CH:8][CH:7]=2)[CH2:32][CH2:33]1)=[O:38])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a suspension of phosphonium bromide 78NLS66 (4.69 g, 10.1 mmol) in THF (100 mL) n-butyllithium (1.6 M in hexane, 6.3 mL, 10.1 mmol) was added at 0° C., giving a deep red solution. After stirring for 1 h at rt, a solution of benzyl 4-oxo-1-piperidinecarboxylate (2.24 g, 9.6 mmol) in THF (10 mL) was added dropwise over 30 min. The mixture was stirred at rt for 20 h, then water was added and the mixture extracted three times with diethylether. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue by silica gel column chromatography, eluting with a stepwise gradient of 0-10% ethyl acetate in n-heptane, afforded the title compound (0.56 g, 17%) as a colourless oil.
Workup
- additionwas added at 0° C.
- customgiving a deep red solution
- stirringThe mixture was stirred at rt for 20 h
- extractionthe mixture extracted three times with diethylether
- dry with materialThe combined organic layers were dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customPurification of the residue by silica gel column chromatography
- washeluting with a stepwise gradient of 0-10% ethyl acetate in n-heptane
Sources & evidence
- ORD record
- ord-ad971e40f24748b8b39d90bb52eb4d53
- Source dataset
- uspto-grants-2005_06
- Patent number
- US06911452B2
Reaction notes
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