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 1 M•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 1 M•HCL in ethanol
7. customrecrystallized twice from methanol

ORD record

ord-d99e8a835dfc4709acf73670ca59eea5

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

USRE037478E1