Methanol → 2-(2-Chloro-6-methyl-benzoylamino)-indane-2-carboxylic acid ethyl ester

HRID 1047803Notes

Reaction equation

HRID 1047803 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.[Cl:25][C:26]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:27]=1[C:28](Cl)=[O:29].CO>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1([NH:15][C:28](=[O:29])[C:27]2[C:31]([CH3:35])=[CH:32][CH:33]=[CH:34][C:26]=2[Cl:25])[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 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylateHCID 223820402-Chloro-6-methylbenzoyl chloride

Product 1

HCID 593142712-(2-Chloro-6-methyl-benzoylamino)-indane-2-carboxylic acid ethyl esterYield 115.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A test tube (25×150 mm) containing a stirring bar and 2-amino-indan-2-carboxylic acid ethyl ester (0.53 g, 2.58 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-chloro-6-methylbenzoyl chloride (5.8 mmol) in dry DCM (4 mL), as prepared above, is added to the reaction tube. After stirring for 18 h, tlc analysis (silica, 10% CH3OH in DCM) indicates complete consumption of the 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 1.07 g of light brown solid. This material is purified by chromatography (silica, 2% to 20% EtOAc in DCM) on the ISCO Companion using a 40 g cartridge. Fractions 6-10 are combined, evaporated and pumped to yield a constant weight 550 mg of white amorphous solid.

Workup

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

Sources & evidence

ORD record
ord-4312170f63134f07bacfc9914a388ba6
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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