Methanol → 2-[(2,2-Difluoro-benzo[1,3]dioxole-4-carbonyl)-amino]-indan-2-carboxylic acid

HRID 1047910Notes

Reaction equation

HRID 1047910 reaction equation
C([O:3][C:4]([C:6]1([NH:15][C:16]([C:18]2[C:26]3[O:25][C:24]([F:28])([F:27])[O: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.O1CCOCC1.CO.O>CO.C(Cl)Cl>[F:28][C:24]1([F:27])[O: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])[CH2:7][C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[CH2:14]3)=[O:17])[C:26]=2[O:25]1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 312751,4-DioxaneHCID 593141652-[(2,2-Difluoro-1,3-benzodioxole-4-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

Product 1

HCID 593143592-[(2,2-Difluoro-benzo[1,3]dioxole-4-carbonyl)-amino]-indan-2-carboxylic acidYield 94%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

A 100 mL flask containing 2-[(2,2-difluoro-1,3-benzodioxole-4-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester (0.38 g, 0.98 mmol) is charged with 1,4-dioxane (6 mL) and MeOH (6 mL). A stirring bar is added and stirring is initiated. After dissolution, water (3 mL) is added followed by the LiOH monohydrate (103 mg, 2.46 mmol). After 70 h, tlc analysis (silica, 10% MeOH/DCM) indicates that the starting material is completely consumed. The pH of the reaction mixture is carefully adjusted to pH 2 by slowly adding dilute aqueous HCl (3%, ˜6 mL). The contents of the flask are poured into a separatory funnel which contains EtOAc (30 mL). The layers are separated. The aqueous layer is extracted with EtOAc (20 mL). The combined organic extracts are washed with water (20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated by pumping to constant weight to give off white solid (0.33 g, 94%).

Workup

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

Sources & evidence

ORD record
ord-5516e07943a64b788dabf210adde8d75
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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