Methyl iodide → methyl 3-(cyclopentyloxy)-4-methoxy-2-(N-methylacetamido)benzoate

HRID 659059Notes

Reaction equation

HRID 659059 reaction equation
[C:1]([NH:4][C:5]1[C:14]([O:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[C:13]([O:21][CH3:22])[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8])(=[O:3])[CH3:2].[H-].[Na+].I[CH3:26]>C1COCC1>[CH:16]1([O:15][C:14]2[C:5]([N:4]([CH3:26])[C:1](=[O:3])[CH3:2])=[C:6]([CH:11]=[CH:12][C:13]=2[O:21][CH3:22])[C:7]([O:9][CH3:10])=[O:8])[CH2:17][CH2:18][CH2:19][CH2:20]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66781936Methyl 2-acetamido-3-(cyclopentyloxy)-4-methoxybenzoate

Product 1

HCID 66781929methyl 3-(cyclopentyloxy)-4-methoxy-2-(N-methylacetamido)benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of methyl 2-acetamido-3-(cyclopentyloxy)-4-methoxybenzoate (1.6 g, 5.2 mmol, Example 1, Step 4) and anhydrous THF (30 mL) was added over 5 min to a mixture of sodium hydride (230 mg, 5.75 mmol) and anhydrous THF (10 mL) at 0° C. under N2. The reaction was allowed to warm to rt and after 20 min, cooled back to 0° C. A solution of iodomethane (1.06 g, 0.0075 mol) and anhydrous THF (10 mL) was added over 3 min. The reaction was allowed to warm to rt and after 30 min, concentrated. The residue was diluted with ethyl acetate (40 mL) and washed with brine (10 mL×2). The organic layer was dried, filtered, and concentrated to give methyl 3-(cyclopentyloxy)-4-methoxy-2-(N-methylacetamido)benzoate: MS (ESI): 322.1.

Workup

  1. temperaturecooled back to 0° C
  2. temperatureto warm to rt and after 30 min
  3. concentrationconcentrated
  4. additionThe residue was diluted with ethyl acetate (40 mL)
  5. washwashed with brine (10 mL×2)
  6. customThe organic layer was dried
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-81f1fdaff76c49f8af3ba2e291451e1d
Source dataset
uspto-grants-2011_12
Patent number
US08080563B2

Reaction notes

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