Methyl iodide → ethyl 2-methyl-2-[5-(methylsulfanyl)pyridin-2-yl]-3-(tetrahydro-2H-pyran-4-yl)propanoate

HRID 1881938Notes

Reaction equation

[CH3:1][S:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([CH2:15][CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:7][CH:8]=1.[CH3:22][Si](C)(C)[N-][Si](C)(C)C.[Li+].CI.[Cl-].[NH4+]>O1CCCC1>[CH3:22][C:9]([C:6]1[CH:5]=[CH:4][C:3]([S:2][CH3:1])=[CH:8][N:7]=1)([CH2:15][CH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of ethyl 2-[5-(methylsulfanyl)pyridin-2-yl]-3-(tetrahydro-2H-pyran-4-yl)propanoate (1.18 g) in dry tetrahydrofuran (7.6 mL) was added lithium hexamethyldisilazide (1.1M tetrahydrofuran solution, 4.49 mL), and the mixture was stirred at 0° C. for 30 min. To the reaction mixture was added methyl iodide (473 μL), and the mixture was stirred at room temperature for 30 min. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the title compound (1.11 g, yield 90%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-hexane (1:2, volume ratio).

Workup

stirringthe mixture was stirred at room temperature for 30 min
extractionthe mixture was extracted with ethyl acetate
washThe extract was washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-6375c445a8e14d33a1085e5451017764
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318746B2

Reaction notes

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