Triethylamine → (R)-methyl 3-(7-chloro-1-oxoisoindolin-2-yl)-2,3-dihydro-1H-indene-5-carboxylate

HRID 1193282Notes

Reaction equation

HRID 1193282 reaction equation
Cl.[CH3:2][O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[CH2:11][CH2:10][C@H:9]2[NH2:15])=[O:5].C[O:17][C:18](=O)[C:19]1[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=1[CH2:26]Br.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:25][C:24]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:19]=1[C:18](=[O:17])[N:15]([C@H:9]1[C:8]3[C:12](=[CH:13][CH:14]=[C:6]([C:4]([O:3][CH3:2])=[O:5])[CH:7]=3)[CH2:11][CH2:10]1)[CH2:26]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 22935208Methyl 2-(bromomethyl)-6-chlorobenzoateHCID 66700566(R)-methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate hydrochloride

Product 1

HCID 59505197(R)-methyl 3-(7-chloro-1-oxoisoindolin-2-yl)-2,3-dihydro-1H-indene-5-carboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3R)-3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-01) (1.757 mmol, 1 eq) was added to a solution of 2-bromomethyl-6-chlorobenzoic acid methyl ester (1 eq) in toluene (5.4 ml) and triethylamine (2.1 eq). The reaction mixture was refluxed for 16 h. Then sat. NaHCO3 solution (20 ml) and ethyl acetate (50 ml) were added to the mixture and the phases were separated. The organic phase was extracted with 0.05 N HCl solution and sat. NaCl solution and dried over MgSO4. Concentration of the organic phase yielded the crude product, which was purified by column chromatography (ethyl acetate:cyclohexane, 3:1). The desired product (R)-methyl 3-(7-chloro-1-oxoisoindolin-2-yl)-2,3-dihydro-1H-indene-5-carboxylate (D-01) was thus obtained. Yield: 72%

Workup

  1. temperatureThe reaction mixture was refluxed for 16 h
  2. customthe phases were separated
  3. extractionThe organic phase was extracted with 0.05 N HCl solution and sat. NaCl solution
  4. dry with materialdried over MgSO4
  5. customConcentration of the organic phase yielded the crude product, which
  6. customwas purified by column chromatography (ethyl acetate:cyclohexane, 3:1)

Sources & evidence

ORD record
ord-58c9fb21c97242f5ae3ca2668c9b3f4e
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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