Methyl iodide → 2-[(2-Isopropoxy-3-methyl-benzoyl)-methyl-amino]-indan-2-carboxylic acid ethyl ester

HRID 1047759Notes

Reaction equation

HRID 1047759 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1([NH:17][C:18](=[O:30])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[C:20]=2[O:26][CH:27]([CH3:29])[CH3:28])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])[CH3:4].[CH3:31]I>C1COCC1>[CH2:3]([O:5][C:6]([C:8]1([N:17]([C:18](=[O:30])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[C:20]=2[O:26][CH:27]([CH3:29])[CH3:28])[CH3:31])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])[CH3:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 593141072-(2-Isopropoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester

Product 1

HCID 593141062-[(2-Isopropoxy-3-methyl-benzoyl)-methyl-amino]-indan-2-carboxylic acid ethyl esterYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of NaH (sodium hydride, 60% dispersion, 86.0 mg, 2.15 mmol)) in anhydrous THF (20 mL) is added dropwise the solution of 2-(2-isopropoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester (6) (410 mg, 1.07 mmol) in THF (5 mL) at 0° C. After stirring for 20 min, methyl iodide (452 μL, 7.26 mmol) is added dropwise and the resulting suspension is warmed up to RT and continued stirring overnight. After being quenched by saturated aqueous solution of ammonium chloride (5 mL), the reaction mixture is diluted in EtOAc (50 mL). The organic layer is separated, washed with water (1×5 mL) and brine (2×5 mL), dried over anhydrous Na2SO4 and concentrated in in vacuo. The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 0%-30% EtOAc in heptane) to give the pure product (118) as a colorless oil (240 mg, 57%).

Workup

  1. stirringcontinued stirring overnight
  2. customAfter being quenched by saturated aqueous solution of ammonium chloride (5 mL)
  3. additionthe reaction mixture is diluted in EtOAc (50 mL)
  4. customThe organic layer is separated
  5. washwashed with water (1×5 mL) and brine (2×5 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated in in vacuo
  8. customThe residue is purified by flash column chromatography (115 g silica gel, gradient elution: 0%-30% EtOAc in heptane)

Sources & evidence

ORD record
ord-809a137d77c24007ba4b79451d0e9c4a
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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