Formaldehyde → 1-Methyl-4-(2,3,4,5,6-pentafluorophenoxy)piperidine
Reaction equation
[F:1][C:2]1[C:14]([F:15])=[C:13]([F:16])[C:12]([F:17])=[C:11]([F:18])[C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.[CH2:19]=O.[BH4-].[Na+]>CO.C(OCC)(=O)C>[CH3:19][N:8]1[CH2:9][CH2:10][CH:5]([O:4][C:3]2[C:11]([F:18])=[C:12]([F:17])[C:13]([F:16])=[C:14]([F:15])[C:2]=2[F:1])[CH2:6][CH2:7]1Participants
Procedure
To a stirring solution of 5.0 g of 4-(2,3,4,5,6-pentafluorophenoxy)piperidine in 50 ml of methanol was added 15 ml of 37% formaldehyde. After refluxing for 1 hour, the solution was cooled to ice bath temperature, treated (portionwise), with 2.5 g of sodium borohydride, and then stirred at ambient temperature for one hour. Evaporation of the volatiles yielded a residue which was taken up in ethyl acetate, washed with water followed by a saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. Concentration afforded an oil which was purified by means of high pressure liquid chromatography (silica gel; elution with 10% methanol/dichloromethane) to yield 4.2 g of 1-methyl-4-(2,3,4,5,6-pentafluorophenoxy)piperidine as an oil. The oil which was dissolved in isopropanol and acidified to pH 1 with etheral hydrogen chloride to precipitate 2.34 g (39%) of the corresponding hydrochloride salt, m.p. 151°-153° C.
Workup
- temperatureAfter refluxing for 1 hour
- temperaturethe solution was cooled to ice bath temperature
- customEvaporation of the volatiles
- customyielded a residue which
- washwashed with water
- dry with materialdried over anhydrous magnesium sulfate
- concentrationConcentration
- customafforded an oil which
- customwas purified by means of high pressure liquid chromatography (silica gel; elution with 10% methanol/dichloromethane)
Sources & evidence
- ORD record
- ord-4ee5be8366c046dcaeac533ab741df12
- Source dataset
- uspto-grants-1990_04
- Patent number
- US04914204
Reaction notes
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