Trifluoroacetic acid → 4-(4-Chlorophenyl)-3,3-dimethylpiperidin-4-ol

HRID 14697Notes

Reaction equation

C(OC([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)([OH:14])[C:10]([CH3:23])([CH3:22])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C:11]2([OH:14])[CH2:12][CH2:13][NH:8][CH2:9][C:10]2([CH3:22])[CH3:23])=[CH:16][CH:17]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a cooled (0° C.) solution of 4-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidine-1-carboxylic acid tert-butyl ester (10.42 g, 30.7 mmol) in methylene chloride (300 mL) was slowly added trifluoroacetic acid (60 mL) over 1.25 hours. The resulting yellow solution was stirred at 0° C. for an additional 1.5 hours. The mixture was concentrated under reduced pressure and the residue dissolved in ethyl acetate (1.2 L), and washed with aqueous sodium hydroxide (1 N, 150 mL). The aqueous layer was extracted with additional ethyl acetate (200 mL) and the combined extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The resulting solid residue was triturated with ether to afford 4-(4-Chloro-phenyl)-3,3-dimethyl-piperidin-4-ol as an off-white solid.

Workup

customover 1.25 hours
concentrationThe mixture was concentrated under reduced pressure
dissolutionthe residue dissolved in ethyl acetate (1.2 L)
washwashed with aqueous sodium hydroxide (1 N, 150 mL)
extractionThe aqueous layer was extracted with additional ethyl acetate (200 mL)
washthe combined extracts were washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe resulting solid residue was triturated with ether

Sources & evidence

ORD record: ord-31f773efdad343bcb763ebdbfc501409
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07732459B2

Reaction notes

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