Benzcatechinborane → 1-Piperidinecarboxylic acid, 3-[(R)-(3-chlorophenyl)hydroxymethyl]-, 1,1-dimethylethyl ester, (3R)-

Temperature

-15 °C

To a solution of (R)-tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylate (5.60 g, 17.29 mmol) and (R)-2-methyl-CBS-oxazaborolidine (1 M in toluene, 9 mL, 9.00 mmol) cooled to −78° C. was added catecholborane (5.6 mL, 54.0 mmol) dropwise. After 20 min, the reaction temperature was allowed to warm to −15° C. and stirred overnight. The reaction was quenched at 0° C. by careful addition of water and diluted with ether. The resulting suspension was filtered through Celite and washed with ether. The filtrate was washed successively with 1 M aq NaOH (3×50 mL), 1 M aq HCl (3×50 mL), satd aq NaHCO3 and brine, and dried over Na2SO4. The solution was filtered, the filtrate was evaporated under vacuum, and the residue was purified by preparative HPLC to afford (R)-tert-butyl 3-((R)-(3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (2.44 g) and (R)-tert-butyl 3-((S)-(3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (1.21 g). MS: 348 (M+Na)+.

1. customThe reaction was quenched at 0° C. by careful addition of water
2. additiondiluted with ether
3. filtrationThe resulting suspension was filtered through Celite
4. washwashed with ether
5. washThe filtrate was washed successively with 1 M aq NaOH (3×50 mL), 1 M aq HCl (3×50 mL)
6. dry with materialdried over Na2SO4
7. filtrationThe solution was filtered
8. customthe filtrate was evaporated under vacuum
9. customthe residue was purified by preparative HPLC

ORD record

ord-350b424e72af4d7d93dcf8366fe840b8

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07872028B2