Water → HCID 22728151, compound

HRID 2086155Notes

Reaction equation

HRID 2086155 reaction equation
[CH:1]1([NH:5][C:6](=[O:27])[C:7]2[CH:12]=[C:11]([O:13][C:14]3[C:19]([CH3:20])=[CH:18][C:17]([N+:21]([O-:23])=[O:22])=[CH:16][C:15]=3[CH3:24])[CH:10]=[CH:9][C:8]=2[O:25][CH3:26])[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].I[CH3:31].O>CN(C)C=O>[CH:1]1([N:5]([CH3:31])[C:6](=[O:27])[C:7]2[CH:12]=[C:11]([O:13][C:14]3[C:19]([CH3:20])=[CH:18][C:17]([N+:21]([O-:23])=[O:22])=[CH:16][C:15]=3[CH3:24])[CH:10]=[CH:9][C:8]=2[O:25][CH3:26])[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 22728145HCID 22728145, compound

Product 1

HCID 22728151HCID 22728151, compoundYield 95.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-Cyclobutyl-5-(2,6-dimethyl-4-nitro-phenoxy)-2-methoxy-benzamide (1.67 grams, 4.51 mmol) in N,N-dimethylformamide (50 mL) at 0° C. under nitrogen was added NaH (60% dispersion in mineral oil, 0.27 grams, 11 mmol). After stirring 30 minutes at 0° C., iodomethane (3.2 g, 23 mmol) was added at 0° C. The reaction mixture was allowed to warm to room temperature and stirred at room temperature for 16 hours, poured into water (450 mL), and extracted with ethyl acetate (3 times 75 mL). The combined organic extracts were washed with water (5 times 200 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (20% ethyl acetate in hexane to 40% ethyl acetate in hexane) to afford the title compound (1.65 grams) as an off white foam. 1H NMR (400 MHz, CDCl3) δ7.96 (s, 2H), 6.80-6.52 (m, 3H, 2 rotomers observed), 5.04, 4.02-3.98 (m, m, 1H, 2 rotomers observed), 3.74, 3.67 (s,s, 3H, 2 rotomers observed), 3.02, 2.75 (s,s, 3H, 2 rotomers observed), 2.25-1.94 (m, 9H, 2 rotomers observed), 1.75-1.41 (m, 3H, 2 rotomers observed). MS (APCI+) Calc: 384.0, Found: 385.2 (M+1).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred at room temperature for 16 hours
  3. extractionextracted with ethyl acetate (3 times 75 mL)
  4. washThe combined organic extracts were washed with water (5 times 200 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (20% ethyl acetate in hexane to 40% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-b72a86b186df4b178752701b087d4563
Source dataset
uspto-grants-2004_04
Patent number
US06723744B2

Reaction notes

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