Methanol → 2-[(2-Chloro-6-methyl-benzoyl)-amino]-indane-2-carboxylic acid

HRID 1047804Notes

Reaction equation

HRID 1047804 reaction equation
C([O:3][C:4]([C:6]1([NH:15][C:16](=[O:25])[C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:24])[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>[Cl:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([CH3:23])[C:17]=1[C:16]([NH:15][C:6]1([C:4]([OH:5])=[O:3])[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:25]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 593142712-(2-Chloro-6-methyl-benzoylamino)-indane-2-carboxylic acid ethyl ester

Product 1

HCID 251609252-[(2-Chloro-6-methyl-benzoyl)-amino]-indane-2-carboxylic acidYield 119.2%

Reagents, catalysts & solvents 1

HCID 21966342Isopropanol methylene chlorideSolvent

Procedure

A 100 mL round bottom flask containing the 2-(2-chloro-6-methyl-benzoylamino)-indane-2-carboxylic acid ethyl ester (0.255 g, 0.712 mmol) is charged with MeOH (15 mL) and a stirring bar is added. Stirring is initiated. After dissolution, water (5 mL) is added and starting material begins to precipitate out. Tetrahydrofuran is added to re-solubilize the starting material. LiOH (90 mg, 2.14 mmol) is added. After 16 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 an addition funnel containing DCM (30 mL). The layers are separated. The aqueous layer is extracted with DCM (20 mL). The combined organic extracts are washed with water (30 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated to yield 280 mg of material. The material is purified by column chromatography (silica, 2% to 15% CH3OH in DCM) using an ISCO Companion and a 12 g cartridge. Fraction 2 is collected and evaporated. After pumping to constant weight, 130 mg of dry white powder is obtained.

Workup

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

Sources & evidence

ORD record
ord-a78533c774b0442c90143dcfb778b1f1
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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