Triethylamine → Diisopropyl Ether

To a mixture of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethylamine (1.17 g, 4.34 mmol) and triethylamine (1.08 g, 10.8 mmol) in chloroform (30 ml) was added nicotinoyl chloride hydrochloride (0.96 g, 5.4 mmol) in one portion. The mixture was stirred for 1 hour at room temperature. The solution was diluted with methylene chloride (DCM) and washed with brine and dried over anhydrous MgSO4. The solution was concentrated and the crude product was purified by flash chromatography over a silica gel column (SiO2, 25 g; eluted with DCM and 1-3% MeOH in DCM). The free base thus purified weighed 1.7 g. This product was treated with 1M· HCl in ethanol and recrystallized twice from methanol:isopropyl ether to yield white crystals, 1.19 g, m.p. 243°-245° C. as a dihydrochloride hydrate.

1. washwashed with brine
2. dry with materialdried over anhydrous MgSO4
3. concentrationThe solution was concentrated
4. customthe crude product was purified by flash chromatography over a silica gel column (SiO2, 25 g; eluted with DCM and 1-3% MeOH in DCM)
5. customThe free base thus purified
6. additionThis product was treated with 1M· HCl in ethanol
7. customrecrystallized twice from methanol

ORD record

ord-debf7cab77a348f2a27f8ebc8116d6a1

Source dataset

uspto-grants-1996_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05571814