Diisopropylethylamine → (R)-Methyl 3-(2-chloro-3-fluorobenzamido)-2,3-dihydro-1H-indene-5-carboxylate

HRID 1193273Notes

Reaction equation

HRID 1193273 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].CCN(C(C)C)C(C)C.[Cl:25][C:26]1[C:34]([F:35])=[CH:33][CH:32]=[CH:31][C:27]=1[C:28](Cl)=[O:29]>ClCCl.C(OCC)(=O)C>[Cl:25][C:26]1[C:34]([F:35])=[CH:33][CH:32]=[CH:31][C:27]=1[C:28]([NH:15][C@H:9]1[C:8]2[C:12](=[CH:13][CH:14]=[C:6]([C:4]([O:3][CH3:2])=[O:5])[CH:7]=2)[CH2:11][CH2:10]1)=[O:29]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 450817242-Chloro-3-fluorobenzoyl chlorideHCID 66700566(R)-methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate hydrochloride

Product 1

HCID 59505666(R)-Methyl 3-(2-chloro-3-fluorobenzamido)-2,3-dihydro-1H-indene-5-carboxylateYield 92%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3R)-3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-01) (0.2 mmol, 1 eq) was dissolved in dichloromethane, and DIPEA (2.5 eq) and 2-chloro-3-fluorobenzoic acid chloride (1.2 eq) were added under a protecting gas atmosphere at 0° C. The reaction mixture was stirred for 2 h at RT. Then the reaction mixture was diluted with ethyl acetate, washed 1× with sat. NaHCO3 solution, 1× with 10% ammonium chloride solution and 1× with sat. NaCl solution, dried over magnesium sulfate and purified by column chromatography (silica gel, cyclohexane:ethyl acetate 4:1). Yield: 92%

Workup

  1. washwashed 1× with sat. NaHCO3 solution, 1× with 10% ammonium chloride solution and 1× with sat. NaCl solution
  2. dry with materialdried over magnesium sulfate
  3. custompurified by column chromatography (silica gel, cyclohexane:ethyl acetate 4:1)

Sources & evidence

ORD record
ord-b240677f5cf349ce9594e4e27bb14765
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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