Water → 1-Boc-4-[6-(trifluoromethyl)-2-pyridyl]piperidin-4-ol

HRID 550818Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[N:3]=1.C([Li])CCC.[C:17]([N:24]1[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].O>O1CCCC1>[C:20]([O:19][C:17]([N:24]1[CH2:29][CH2:28][C:27]([OH:30])([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[N:3]=2)[CH2:26][CH2:25]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]

Participants

Conditions

Temperature: -78 °C

Procedure

A mixture of 2-bromo-6-(trifluoromethyl)pyridine (300 mg, 1.33 mmol) in tetrahydrofuran (10 mL) under a nitrogen atmosphere cooled to −78° C. was treated with n-butyl lithium (2M solution in tetrahydrofuran, 0.83 mL, 1.33 mmol). The mixture was stirred at −78° C. for 15 min. At this time, the reaction was treated with 1-boc-4-piperidone (265 mg, 1.33 mmol). The mixture was then allowed to slowly warm to 25° C. and was stirred at 25° C. for 1 h. At this time, the reaction was poured into water. The aqueous layer was extracted with ethyl acetate. The organics were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 4′-hydroxy-6-trifluoromethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (450 mg, 98%) as a yellow oil; LRMS for C16H21F3N2O3 (M+H)+ at m/z=346. The NMR spectrum obtained on the sample is compatible with its structure.

Workup

temperatureto slowly warm to 25° C.
stirringwas stirred at 25° C. for 1 h
extractionThe aqueous layer was extracted with ethyl acetate
washThe organics were washed with a saturated aqueous sodium chloride solution
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-983e091297c04e8b88ba9aed219ec45e
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07947692B2

Reaction notes

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