Methanol → 2-[(2,2-Dimethyl-2,3-dihydro-benzofuran-7-carbonyl)-amino]-indan-2-carboxylic acid

HRID 1047801Notes

Reaction equation

HRID 1047801 reaction equation
C([O:3][C:4]([C:6]1([NH:15][C:16]([C:18]2[C:26]3[O:25][C:24]([CH3:28])([CH3:27])[CH2:23][C:22]=3[CH:21]=[CH:20][CH:19]=2)=[O:17])[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])C.CO.O.[Li+].[OH-]>CC(O)C.C(Cl)Cl>[CH3:27][C:24]1([CH3:28])[CH2:23][C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([C:16]([NH:15][C:6]3([C:4]([OH:5])=[O:3])[CH2:14][C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[CH2:7]3)=[O:17])[C:26]=2[O:25]1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 593143462-[(2,2-Dimethyl-2,3-dihydro-benzofuran-7-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

Product 1

HCID 593143572-[(2,2-Dimethyl-2,3-dihydro-benzofuran-7-carbonyl)-amino]-indan-2-carboxylic acidYield 111%

Reagents, catalysts & solvents 1

HCID 21966342Isopropanol methylene chlorideSolvent

Procedure

A 50 mL round bottom flask containing the 2-[(2,2-dimethyl-2,3-dihydro-benzofuran-7-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester (0.45 g, 1.179 mmol) is charged with MeOH (25 mL) and a stirring bar is added. Stirring is initiated. After dissolution, water (8 mL) and the LiOH (108 mg, 2.58 mmol) are added. After 56 h, tlc analysis (silica, 5% i-PrOH/DCM) indicates that the starting material is completely consumed. The pH of the reaction mixture is carefully adjusted to pH 3 by slowly adding dilute aqueous HCl (3%, ˜20 mL). The contents of the flask are poured into a reparatory funnel containing EtOAc (30 mL). The layers are separated. The aqueous layer is extracted with EtOAc (20 mL). The combined organic extracts are washed with water (30 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated. Pumping to constant weight gives 460 mg of material. The sample is purified by column chromatography (silica, 2% to 15% CH3OH in DCM) using an ISCO Companion and a 12 g cartridge. Fraction 3 is collected and evaporated. After pumping to constant weight, 375 mg (90%) of a dry white powder is obtained.

Workup

  1. additionis added
  2. customis completely consumed
  3. additionby slowly adding dilute aqueous HCl (3%, ˜20 mL)
  4. additionThe contents of the flask are poured into a reparatory funnel
  5. additioncontaining EtOAc (30 mL)
  6. customThe layers are separated
  7. extractionThe aqueous layer is extracted with EtOAc (20 mL)
  8. washThe combined organic extracts are washed with water (30 mL) and brine (20 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-75f0bbd19a3b408bbdd47079b9417008
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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