Methyl iodide → 2-[Methyl-(5,6,7,8-tetrahydro-naphthalene-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

HRID 1047761Notes

Reaction equation

HRID 1047761 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1([NH:17][C:18]([C:20]2[C:29]3[CH2:28][CH2:27][CH2:26][CH2:25][C:24]=3[CH:23]=[CH:22][CH:21]=2)=[O:19])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])[CH3:4].[CH3:30]I>C1COCC1>[CH2:3]([O:5][C:6]([C:8]1([N:17]([CH3:30])[C:18]([C:20]2[C:29]3[CH2:28][CH2:27][CH2:26][CH2:25][C:24]=3[CH:23]=[CH:22][CH:21]=2)=[O:19])[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 593141592-[(5,6,7,8-Tetrahydro-naphthalene-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

Product 1

HCID 593141972-[Methyl-(5,6,7,8-tetrahydro-naphthalene-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of NaH (sodium hydride, 60% dispersion, 124 mg, 3.08 mmol) in anhydrous THF (20 mL) is added dropwise the solution of 2-[(5,6,7,8-tetrahydro-naphthalene-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester (37) (280 mg, 0.77 mmol) in THF (5 mL) at 0° C. After stirring for 20 min, methyl iodide (377 μL, 6.05 mmol) is added dropwise and the resulting suspension is warmed up to RT and continued stirring overnight. After being quenched by saturated ammonium chloride aqueous solution (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 a pure product (120) as a colorless semisolid (250 mg, 86%).

Workup

  1. stirringcontinued stirring overnight
  2. customAfter being quenched by saturated ammonium chloride aqueous solution (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-6d0db7c7a9704ccab19f3298a7a0185f
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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