Aluminium lithium hydride → Tert-butyl 4-(chloromethyl)-4-(hydroxymethyl)piperidine-1-carboxylate

Temperature

0 °C

A solution of 1-tert-butyl 4-methyl 4-(chloromethyl)piperidine-1,4-dicarboxylate (11.7 g, 40.2 mmol) in anhydrous THF (100 mL) was cooled to 0° C. Lithium aluminum hydride (1N in THF, 44.3 mL, 44.3 mmol), was added slowly (15-20 min) and the solution was stirred at 0° C. for 25 minutes. The mixture was quenched by adding water (1.8 mL) dropwise with great caution. Aqueous 1N NaOH (1.8 mL) was added dropwise, and the mixture was stirred for 5 minutes. The cooling bath was removed, the solids were filtered off, and the cake was washed with Et2O (2×100 mL). The filtrate was washed with water (2×100 mL), brine (100 mL), dried (Na2SO4) and concentrated under reduced pressure to give tert-butyl 4-(chloromethyl)-4-(hydroxymethyl)piperidine-1-carboxylate as a solid (9.96 g, 93.8%). 1H NMR (CDCl3) δ 1.43 (s, 9H), 1.48-1.55 (m, 4H), 3.36-3.41 (m, 4H), 3.57 (s, 2H), 3.59 (br s, 2H).

1. customThe mixture was quenched
2. additionby adding water (1.8 mL) dropwise with great caution
3. additionAqueous 1N NaOH (1.8 mL) was added dropwise
4. stirringthe mixture was stirred for 5 minutes
5. customThe cooling bath was removed
6. filtrationthe solids were filtered off
7. washthe cake was washed with Et2O (2×100 mL)
8. washThe filtrate was washed with water (2×100 mL), brine (100 mL)
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated under reduced pressure

ORD record

ord-dcc24d47cd1440279b2a02031761bb07

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09370516B2