Potassium Hydroxide → (R)-3-(7-chloro-1-oxoisoindolin-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid

HRID 1193292Notes

Reaction equation

HRID 1193292 reaction equation
[OH-].[K+].[Cl:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[C:11](=[O:13])[N:10]([C@H:14]1[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:23]([O:25]C)=[O:24])[CH:21]=3)[CH2:16][CH2:15]1)[CH2:9]2>C(O)C.O>[Cl:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[C:11](=[O:13])[N:10]([C@H:14]1[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:23]([OH:25])=[O:24])[CH:21]=3)[CH2:16][CH2:15]1)[CH2:9]2

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 59505197(R)-methyl 3-(7-chloro-1-oxoisoindolin-2-yl)-2,3-dihydro-1H-indene-5-carboxylate

Product 1

HCID 59505726(R)-3-(7-chloro-1-oxoisoindolin-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

KOH (1 mol/l aq) (2 eq) was added to a suspension of (R)-methyl 3-(7-chloro-1-oxoisoindolin-2-yl)-2,3-dihydro-1H-indene-5-carboxylate (D-01) (0.42 mmol, 1 eq) in a mixture of ethanol (4 ml) and water (1.6 ml). The reaction mixture was stirred overnight at RT. Ethanol was removed in vacuo, and the residue was taken up in diethyl ether and water. The phases were separated, and the aqueous phase was adjusted to pH 3 with 1N HCl. The aqueous phase was extracted with ethyl acetate (3×) and the combined organic phases were dried over sodium sulfate. After concentration, the desired product (R)-3-(7-chloro-1-oxoisoindolin-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (G-01) was obtained. Yield: 82%

Workup

  1. customEthanol was removed in vacuo
  2. customThe phases were separated
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. concentrationAfter concentration

Sources & evidence

ORD record
ord-6f0cb9feaf0549e58dea8c2e72c55dd5
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

Loading…