1-Methyl-4-piperidone → 1-Methyl-4-(5-(2-methyl-1,3-dioxolan-2-yl)pyridin-2-yl)piperidin-4-ol

HRID 40855

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:13])[O:12][CH2:11][CH2:10][O:9]2)=[CH:4][N:3]=1.[Li]CCCC.[CH3:19][N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1>O1CCCC1>[CH3:19][N:20]1[CH2:25][CH2:24][C:23]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3([CH3:13])[O:12][CH2:11][CH2:10][O:9]3)=[CH:4][N:3]=2)([OH:26])[CH2:22][CH2:21]1

Participants

Conditions

Temperature: -78 °C

Procedure

2-bromo-5-(2-methyl-1,3-dioxolan-2-yl)pyridine (500 mg, 2.048 mmol) (described in the literature: Bioorg. Med. Chem., 2005, 13, 6763) was dissolved in anhydrous tetrahydrofuran (10 mL) and cooled to −78° C. under nitrogen. n-BuLi (901.2 μL of 2.5 M, 2.253 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for 30 minutes. 1-Methyl-4-piperidone (602.6 mg, 655.0 μL, 5.325 mmol) was added and the reaction was allowed to stir at −78° C. for 20 minutes then warmed slowly to ambient temperature. The reaction mixture was stirred at room temperature for 18 hours and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography to afford the title compound as a sticky orange solid (483.4 mg, 85% yield).

Workup

stirringto stir at −78° C. for 20 minutes
temperaturethen warmed slowly to ambient temperature
stirringThe reaction mixture was stirred at room temperature for 18 hours
concentrationconcentrated in vacuo
customThe residue was purified on silica gel by flash column chromatography

Sources & evidence

ORD record: ord-91cc42242a62446c90786896b5303af2
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530489B2

Linked notes

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