Methylparaben → Benzoic acid, 4-[(1-methyl-4-piperidinyl)oxy]-, methyl ester
Reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:28][O:29][C:30](=[O:38])[C:31]1[CH:36]=[CH:35][C:34](O)=[CH:33][CH:32]=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:28][O:29][C:30](=[O:38])[C:31]1[CH:36]=[CH:35][C:34]([O:8][CH:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)=[CH:33][CH:32]=1Participants
Procedure
To a solution of 1-methyl-piperidin-4-ol (6.8 g. 59 mmoles), PPh3 (triphenylphosphine, 15.5 g, 59 mmoles) and 4-hydroxy-benzoic acid methyl ester (6 g, 39 mmoles) in THF (150 ml) at 0° C., diethyl azodicarboxylate (9.5 ml, 59 mmoles) in THF (30 ml) was slowly added. The reaction mixture was allowed to warm to room temperature over a period of 24 hours. It was then evaporated and the residue redissolved in 5% aqueous citric acid (700 ml). The solution was washed with ethyl acetate (3×250 ml), made alkaline with concentrated NH4OH (pH˜8) and then extracted with dichloromethane (3×250 ml). The combined dichloromethane extracts were washed with brine, dried and evaporated to give an oil which was purified by flash chromatography on silica gel using dichloromethane-MeOH (90:10) as eluent, to give the title compound as a yellow oil (7.4 g, 75%).
Workup
- customIt was then evaporated
- dissolutionthe residue redissolved in 5% aqueous citric acid (700 ml)
- washThe solution was washed with ethyl acetate (3×250 ml)
- extractionextracted with dichloromethane (3×250 ml)
- washThe combined dichloromethane extracts were washed with brine
- customdried
- customevaporated
- customto give an oil which
- customwas purified by flash chromatography on silica gel
Sources & evidence
- ORD record
- ord-2be8938c04ac4648aa15e29835774ca9
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08481585B2
Reaction notes
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