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-b07b2d2daa1b4cad9fe4ec5dad5158c5

Source dataset

uspto-grants-1996_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05580879