Dimethylformamide → 2-(3-Acetoxy-4-trifluoromethyl-benzoylamino)-indane-2-carboxylic acid methyl ester

HRID 2405249Notes

Reaction equation

HRID 2405249 reaction equation
[C:1]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][C:13]=1[C:14]([F:17])([F:16])[F:15])[C:8]([OH:10])=O)(=[O:3])[CH3:2].C(Cl)(=O)C(Cl)=O.CN(C=O)C.Cl.[CH3:30][O:31][C:32]([C:34]1([NH2:43])[CH2:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:35]1)=[O:33]>C(Cl)Cl.C(=O)([O-])O.[Na+]>[CH3:30][O:31][C:32]([C:34]1([NH:43][C:8](=[O:10])[C:7]2[CH:11]=[CH:12][C:13]([C:14]([F:17])([F:16])[F:15])=[C:5]([O:4][C:1](=[O:3])[CH3:2])[CH:6]=2)[CH2:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:35]1)=[O:33]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 236167943-Acetoxy-4-trifluoromethyl-benzoic acidHCID 45074056methyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate hydrochloride

Product 1

HCID 670766942-(3-Acetoxy-4-trifluoromethyl-benzoylamino)-indane-2-carboxylic acid methyl esterYield 24%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 2.7 g (10.9 mmol) of the compound of step 1 in 16.3 ml of a 2 M solution of oxalyl chloride in DCM (32.6 mmol), 80 mg of DMF were added and the mixture was stirred for 30 min at room temperature. The solvent was evaporated, 20 ml of DCM were added and the mixture was evaporated again. The residue was dissolved in 20 ml of DCM and the solution added within 5 min at 0° C. to a solution of 2.48 g (10.9 mmol) of 2-amino-indane-2-carboxylic acid methyl ester hydrochloride in 50 ml of DCM and 30 ml of a saturated sodium hydrogencarbonate solution. After stirring overnight, the phases were separated, the organic phase was dried over sodium sulfate, evaporated, and the residue was purified by silica gel chromatography (HEP/EA gradient). 1.1 g of the title compound were obtained.

Workup

  1. customThe solvent was evaporated
  2. addition20 ml of DCM were added
  3. customthe mixture was evaporated again
  4. dissolutionThe residue was dissolved in 20 ml of DCM
  5. stirringAfter stirring overnight
  6. customthe phases were separated
  7. dry with materialthe organic phase was dried over sodium sulfate
  8. customevaporated
  9. customthe residue was purified by silica gel chromatography (HEP/EA gradient)

Sources & evidence

ORD record
ord-149a4ba977094ac7b6c88e3d763b02b6
Source dataset
uspto-grants-2014_08
Patent number
US08802720B2

Reaction notes

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