Hydrochloric Acid → 4-(6-Chloropyridin-3-yl)piperidin-4-ol

HRID 1675025Notes

Reaction equation

Cl.[Cl:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2([OH:22])[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1>C(OCC)(=O)C.CCOCC>[Cl:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2([OH:22])[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]2)=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 50 °C

Procedure

HCl (4M in dioxan, 4.22 mL, 16.88 mmol) was added in one portion to a stirred suspension of tert-butyl 4-(6-chloropyridin-3-yl)-4-hydroxypiperidine-1-carboxylate (1.32 g, 4.22 mmol) in ethyl acetate (20 mL) at ambient temperature. The resulting mixture was stirred at 50° C. for 90 minutes then cooled to room temperature, diluted with ether (20 mL) and filtered. The filtered solid was washed with ether and dried then taken up in methanol, applied to an SCX column and eluted with methanol followed by 2M ammonia in methanol. Product-containing fractions were combined and evaporated then purified by flash silica chromatography, elution gradient 10 to 20% 2M ammonia in methanol in DCM. Pure fractions were evaporated to dryness to afford 4-(6-chloropyridin-3-yl)piperidin-4-ol (0.43 g, 48%) as a pale orange solid.

Workup

temperaturethen cooled to room temperature
filtrationfiltered
washThe filtered solid was washed with ether
customdried
washeluted with methanol
customevaporated
customthen purified by flash silica chromatography, elution gradient 10 to 20% 2M ammonia in methanol in DCM
customPure fractions were evaporated to dryness

Sources & evidence

ORD record: ord-a303cd953d89417d96a8f5eac590513d
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003649B2

Reaction notes

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