Water → HCID 131725381, compound

To a solution of isonipecotamide (2 g, 15.6 mmol) and pivalaldehyde (2.0 mL, 18.7 mmol) in tetrahydrofuran (200 mL) was added titanium(IV) isopropoxide (4.6 mL, 15.6 mmol) and the mixture was stirred at room temperature for 21 h under nitrogen. Solvent was removed, the residue was dissolved in ethanol (60 mL) and sodium cyanoborohydride (1.6 g, 23.4 mmol) was added at room temperature. After stirring for 89 h, water (30 mL) was added, obtained precipitate was removed by filtration and the filtrate was concentrated. The residue was treated with water (30 mL) basified with 2 N sodium hydroxide, extracted with dichloromethane (30 mL×3) and washed with brine (30 mL). The organic extracts were dried over sodium sulfate and concentrated to give a white solid, which was purified by flash column chromatography on silica gel eluting with dichloromethane/methanol/25% ammonia solution (20:1:0.1) to affoad 715 mg (23%) of the title compound as a white solid.

1. customSolvent was removed
2. dissolutionthe residue was dissolved in ethanol (60 mL)
3. stirringAfter stirring for 89 h
4. customobtained precipitate
5. customwas removed by filtration
6. concentrationthe filtrate was concentrated
7. additionThe residue was treated with water (30 mL)
8. extractionextracted with dichloromethane (30 mL×3)
9. washwashed with brine (30 mL)
10. dry with materialThe organic extracts were dried over sodium sulfate
11. concentrationconcentrated
12. customto give a white solid, which
13. customwas purified by flash column chromatography on silica gel eluting with dichloromethane/methanol/25% ammonia solution (20:1:0.1) to affoad 715 mg (23%) of the title compound as a white solid

ORD record

ord-c8ee29894fc5405cbbc6c0568448758b

Source dataset

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07012080B2