Methyl iodide → Ethyl 4-(6-bromopyridin-3-yl)-2-methyl-2-(methylsulfonyl)butanoate

HRID 533526Notes

Reaction equation

HRID 533526 reaction equation
CI.[C:3](=O)([O-])[O-].[K+].[K+].[Br:9][C:10]1[N:15]=[CH:14][C:13]([CH2:16][CH2:17][CH:18]([S:24]([CH3:27])(=[O:26])=[O:25])[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:12][CH:11]=1>CN(C=O)C.Cl>[Br:9][C:10]1[N:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]([CH3:3])([S:24]([CH3:27])(=[O:26])=[O:25])[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:12][CH:11]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 86668760HCID 86668760, compound

Product 1

HCID 86668759Ethyl 4-(6-bromopyridin-3-yl)-2-methyl-2-(methylsulfonyl)butanoateYield 66.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of methyl iodide (633 uL, 10.2 mmol, 2.2 equiv), potassium carbonate (895 mg, 6.5 mmol, 1.4 equiv), and ethyl 4-(6-bromopyridin-3-yl)-2-(methylsulfonyl)butanoate (1620 mg, 4.6 mmol, 1.0 equiv) in DMF (15 mL) was allowed to stir at room temperature overnight. The reaction was diluted with 0.5 M hydrochloric acid (220 mL) and was extracted with ethyl acetate (3×80 mL). The combined organic layers were washed with water (170 mL) and sodium thiosulfate (170 mL, 10% aq. solution), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (7:3 heptane/ethyl acetate) to provide the title compound as a white solid (1107 mg, 66%). MS (LCMS) m/z 364.1 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.33 (t, J=7.22 Hz, 3H) 1.69 (s, 3H) 2.12-2.23 (m, 1H) 2.39-2.59 (m, 2H) 2.69-2.79 (m, 1H) 3.02 (s, 3H) 4.27 (qd, J=7.16, 2.73 Hz, 2H) 7.35-7.43 (m, 2H) 8.20 (d, J=1.95 Hz, 1H).

Workup

  1. extractionwas extracted with ethyl acetate (3×80 mL)
  2. washThe combined organic layers were washed with water (170 mL) and sodium thiosulfate (170 mL, 10% aq. solution)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by flash chromatography on silica gel (7:3 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-6ec0d5ba93404672ad82f228d4630a88
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

Loading…