Methanol → tert-butyl 3-((R)-(3-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate

To a solution of 1 M R-CBS-oxazaborolidine in toluene (33 mL, 33 mmol, 0.15 eq) and 10 M BH3 in THF (22 mL, 0.22 mol, 1.0 eq) at −15° C. under nitrogen was added dropwise a solution of (R)-tert-butyl 3-(3-fluorobenzoyl)piperidine-1-carboxylate (67.5 g, 0.22 mol) in anhydrous THF (300 mL). After addition, the reaction mixture was stirred for 1 hr at rt. Methanol (200 mL) was added dropwise carefully at 0° C. The solvent was removed under reduced pressure to provide the crude product. The crude product was dissolved in ethyl acetate until the alcohol was just dissolved (about 5 mL/1 g), the solvent was removed on the rotary evaporator until a few crystals appeared. To the above solution was added petroleum ether (about 300 mL) under stirring, which was allowed to stir at rt for 2 hr and then filtered, the crystals were washed with petroleum ether and re-crystallized to afford the pure R)-tert-butyl 3-((R)-(3-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (26 g, 39%).

1. additionAfter addition
2. customThe solvent was removed under reduced pressure
3. customto provide the crude product
4. dissolutionwas just dissolved (about 5 mL/1 g)
5. customthe solvent was removed on the rotary evaporator until a few crystals
6. additionTo the above solution was added petroleum ether (about 300 mL)
7. stirringunder stirring
8. stirringto stir at rt for 2 hr
9. filtrationfiltered
10. washthe crystals were washed with petroleum ether
11. customre-crystallized

ORD-Eintrag

ord-487b75a7432c4cdf83615a2650e31729

Quelldatensatz

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08487108B2