tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 59833545, compound

HRID 1261667Notes

Reaction equation

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

Participants

Conditions

Temperature: -78 °C

Procedure

To a slightly cloudy solution of 3-bromo-5-(trifluoromethyl)pyridine (2.20 g, 30% purity, 2.92 mmol) in dry methylene chloride (15.0 mL) at −78° C. was added a 1.6 M solution of n-butyllithium in hexanes (1.99 mL). After being stirred for 30 min at −78° C., a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (0.534 g, 2.65 mmol) in dry methylene chloride (3.0 mL) was added dropwise. The reaction was stirred at −78° C. for 1.5 h and quenched with aqueous NH4Cl. The resulting solution was extracted with methylene chloride three times. The combined organic layers were dried, filtered and concentrated. The residue was purified by column chromatography on silica gel (50:50 EtOAc/hexanes) to give 330 mg (25%) of desired product as a yellow oil. LC-MS calculated for C16H21F3N2O3: (M+H) 347; found 247.1 (M-Boc+1).

Workup

stirringThe reaction was stirred at −78° C. for 1.5 h
customquenched with aqueous NH4Cl
extractionThe resulting solution was extracted with methylene chloride three times
customThe combined organic layers were dried
filtrationfiltered
concentrationconcentrated
customThe residue was purified by column chromatography on silica gel (50:50 EtOAc/hexanes)

Sources & evidence

ORD record: ord-d54a4358277e4e8eb84eb302f9a81ef5
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08470827B2

Reaction notes

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