Methanol → 2-[(2,2-Dimethyl-2,3-dihydro-benzofuran-7-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

HRID 1047800Notes

Reaction equation

HRID 1047800 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH2:15])[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])[CH3:2].CCN(C(C)C)C(C)C.[CH3:25][C:26]1([CH3:38])[CH2:30][C:29]2[CH:31]=[CH:32][CH:33]=[C:34]([C:35](Cl)=[O:36])[C:28]=2[O:27]1.CO>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1([NH:15][C:35]([C:34]2[C:28]3[O:27][C:26]([CH3:38])([CH3:25])[CH2:30][C:29]=3[CH:31]=[CH:32][CH:33]=2)=[O:36])[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 27954702,2-Dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chlorideHCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate

Product 1

HCID 593143462-[(2,2-Dimethyl-2,3-dihydro-benzofuran-7-carbonyl)-amino]-indan-2-carboxylic acid ethyl esterYield 77.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A test tube (25×150 mm) containing a stirring bar and 2-amino-indane-2-carboxylic acid ethyl ester (0.5 g, 2.436 mmol) is charged with dry DCM (3 mL). Stirring is initiated. After dissolution, the DIPEA (1.50 mL, 8.6 mmol) and 4-dimethylaminopyridine (2 mg, 17 μmol) are added. A solution of 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride (0.73 g, 3.47 mmol) in dry DCM (4 mL) is added to the reaction tube. After stirring for 18 h, tlc analysis (silica, 10% CH3OH in DCM) indicates complete consumption of the starting amine. The reaction mixture is diluted with DCM (10 mL) and washed with 5% aqueous HCl (2×5 mL) and brine (5 mL), dried over MgSO4 filtered and evaporated by pumping to constant weight gives 0.72 g of a light brown gum. This material is purified by chromatography (silica, 0% to 20% EtOAc in DCM) on the ISCO Companion using a 40 g cartridge (silica). Fractions 17-22 are combined, evaporated and pumped to a constant weight to provide 0.62 g (67%) of a glassy solid.

Workup

  1. additionA test tube (25×150 mm) containing a stirring bar
  2. dissolutionAfter dissolution
  3. stirringAfter stirring for 18 h
  4. customconsumption of the starting amine
  5. additionThe reaction mixture is diluted with DCM (10 mL)
  6. washwashed with 5% aqueous HCl (2×5 mL) and brine (5 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-5e803db07bec4ba4ac561105a933a1ef
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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