4-Methylpiperidine → HCID 23104916, compound

11 g (50 mmol) of 3-chlorosulphonylbenzoic acid in suspension in dichloromethane (300 ml) is treated with 12.4 g (125 mmol) of 4-methylpiperidine and the reaction mixture is maintained under stirring at ambient temperature overnight. The resulting solution is washed successively with a 10% aqueous solution of citric acid and a saturated solution of sodium chloride, followed by drying (Na2SO4) and concentrating under reduced pressure in order to produce a colourless viscous residue. The latter is taken up in methanol and, whilst maintaining the temperature between 0° C. and 10° C., is titrated by trimethylsilyldiazomethane until a characteristic yellow coloration persists. The excess reagent is destroyed with a few drops of formic acid, and the reaction medium is concentrated under reduced pressure. The traces of acid and methanol are eliminated by two azeotropic evaporations under reduced pressure with toluene. The residue, taken up in tetrahydrofuran (300 ml), is treated with lithium borohydride (2N in THF, 30 ml). The reaction medium is taken to reflux for 2 hours then cooled down and hydrolyzed with a saturated solution of ammonium chloride. The resulting mixture is extracted with ethyl acetate then the organic phase is washed with a saturated solution of sodium chloride, followed by drying (Na2SO4) and concentrating under reduced pressure. The residue is purified on a silica column (eluent: 5% acetone in dichloromethane) in order to produce the expected benzyl alcohol in the form of a white solid.

1. temperaturethe reaction mixture is maintained
2. washThe resulting solution is washed successively with a 10% aqueous solution of citric acid
3. dry with materialby drying (Na2SO4)
4. concentrationconcentrating under reduced pressure in order
5. customto produce a colourless viscous residue
6. temperaturewhilst maintaining the temperature between 0° C. and 10° C.
7. customThe excess reagent is destroyed with a few drops of formic acid
8. concentrationthe reaction medium is concentrated under reduced pressure
9. additionis treated with lithium borohydride (2N in THF, 30 ml)
10. temperatureto reflux for 2 hours
11. temperaturethen cooled down
12. extractionThe resulting mixture is extracted with ethyl acetate
13. washthe organic phase is washed with a saturated solution of sodium chloride
14. dry with materialby drying (Na2SO4)
15. concentrationconcentrating under reduced pressure
16. customThe residue is purified on a silica column (eluent: 5% acetone in dichloromethane) in order

ORD record

ord-1681213617ad44be88da505ae0b3d351

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07196084B2