Carbonocyanidic acid, methyl ester → HCID 117665483, compound

HRID 1482451Notes

Reaction equation

HRID 1482451 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)=[C:15]2[C:19]=1[C:18](=[O:20])[CH2:17][CH2:16]2.C([C:33]([O:35][CH3:36])=[O:34])#N>C1COCC1>[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=2)=[C:15]2[C:19]=1[C:18](=[O:20])[CH:17]([C:33]([O:35][CH3:36])=[O:34])[CH2:16]2

Participants

5

Reactant 3

HCID 28660Carbonocyanidic acid, methyl esterHCID 2724682Lithium diisopropylamideHCID 117665532HCID 117665532, compound

Product 1

HCID 117665483HCID 117665483, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of lithium diisopropylamide (2.0 M in THF, 0.18 mL, 0.36 mmol) was added to a solution of 7-methoxy-4-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-one (103 mg, 0.34 mmol) in THF (1.1 mL) at −78° C. After 1 h at −78° C., methyl cyanoformate (40 μL, 0.50 mmol) was added and the reaction mixture was allowed to warm to room temperature. After stirring at room temperature overnight, the reaction was quenched with saturated aqueous NH4Cl (25 mL) and extracted with EtOAc (3×40 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The resulting crude residue was purified by combiflash (12 g column, hexanes→EtOAc, gradient) to afford 26 mg (21%) of methyl 7-methoxy-1-oxo-4-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-indene-2-carboxylate.

Workup

  1. customthe reaction was quenched with saturated aqueous NH4Cl (25 mL)
  2. extractionextracted with EtOAc (3×40 mL)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting crude residue was purified by combiflash (12 g column, hexanes→EtOAc, gradient)

Sources & evidence

ORD record
ord-7c67a468ac044ae1999adfd3aa9efc0a
Source dataset
uspto-grants-2016_08
Patent number
US09415027B2

Reaction notes

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