Tert-butyl 4-(hydroxy(pyridin-3-yl)methyl)piperidine-1-carboxylate → Piperidin-4-yl(pyridin-3-yl)methanol

HRID 862726Notes

Reaction equation

CC(C)(OC([N:7]1[CH2:12][CH2:11][CH:10]([CH:13]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[OH:14])[CH2:9][CH2:8]1)=O)C>FC(F)(F)C(O)=O>[NH:7]1[CH2:12][CH2:11][CH:10]([CH:13]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[OH:14])[CH2:9][CH2:8]1

Participants

Conditions

Temperature: 0 °C

Procedure

Trifluoroacetic acid (100 mL) was cooled to 0° C. and added to a flask containing 1-(1,1-dimethylethyl-oxycarbonyl)piperidin-4-yl-pyridin-3-ylmethanol (20.4 g, 69.77 mmol). Vigorous gas evolution was observed. The mixture was stirred at 0° C. until judged complete by TLC. The excess trifluoroacetic acid was removed in vacuo, and the resulting residue was dissolved in water (50 mL). The aqueous solution was cooled to 0° C. and basified to pH~ 12 by addition of sodium hydroxide pellets. The product was isolated by extraction of the aqueous solution with dichloromethane (10×100 mL). The dichloromethane was evaporated to leave the title compound as an off white solid (12.06 g, 62.73 mmol, 90%). 1H NMR(d6 -DMSO): δ8.45 (m, 2H, H--C(2'), H--C(6')), 7.66 (brd, J=7.8 Hz, 1H, H--C(4')), 7.34 (dd, J=4.8, 7.8 Hz, 1H, H--C(3')), 4.29 (d, J=6.7 Hz, 1H, CHOH), 2.67 (m, 2H, eq-H--C(2)), 2.27 (m, 2H, ax-H--C(2)), 1.70 (br, 1H, NH), 1.52 (m, 1H, H--C(4)), 1.10-1.00 (m, 4H, H--C(3)).

Workup

additionadded to a flask
customThe excess trifluoroacetic acid was removed in vacuo
dissolutionthe resulting residue was dissolved in water (50 mL)
temperatureThe aqueous solution was cooled to 0° C. and basified to pH~ 12 by addition of sodium hydroxide pellets
customThe product was isolated by extraction of the aqueous solution with dichloromethane (10×100 mL)
customThe dichloromethane was evaporated

Sources & evidence

ORD record: ord-09c12b88c99846d6bd4d974b426d4754
Source dataset: uspto-grants-1998_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05719166

Reaction notes

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