Methanol → 2-(2-Cyclobutoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid

HRID 1047806Notes

Reaction equation

HRID 1047806 reaction equation
C([O:3][C:4]([C:6]1([NH:15][C:16](=[O:29])[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:18]=2[O:24][CH:25]2[CH2:28][CH2:27][CH2:26]2)[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])C.O1CCOCC1.CO.[Li+].[OH-]>CC(O)C.C(Cl)Cl.O>[CH:25]1([O:24][C:18]2[C:19]([CH3:23])=[CH:20][CH:21]=[CH:22][C:17]=2[C:16]([NH:15][C:6]2([C:4]([OH:5])=[O:3])[CH2:7][C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH2:14]2)=[O:29])[CH2:28][CH2:27][CH2:26]1

Participants

7

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 312751,4-DioxaneHCID 593140752-(2-Cyclobutoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester

Product 1

HCID 251602822-(2-Cyclobutoxy-3-methyl-benzoylamino)-indan-2-carboxylic acidYield 98.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21966342Isopropanol methylene chlorideSolvent

Procedure

A 50 mL flask containing the 2-[(2-cyclobutoxy-3-methyl-benzoyl)-amino]-indan-2-carboxylic acid ethyl ester (1.72 g, 4.37 mmol) is charged with 1,4-dioxane (16 mL) and MeOH (16 mL). A stirring bar is added and stirring is initiated. After dissolution, water (8 mL) is added followed by the LiOH (458 mg, 10.91 mmol). After 20 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 2 by slowly adding dilute aqueous HCl (3%, ˜25 mL). The contents of the flask are poured into a separatory funnel containing EtOAc (60 mL). The layers are separated. The aqueous layer is extracted with EtOAc (30 mL). The combined organic extracts are washed with water (35 mL) and brine (35 mL), dried over MgSO4, filtered and concentrated. Pumping to constant weight gives 1.58 g of a white solid.

Workup

  1. additionA stirring bar is added
  2. additionis added
  3. customis completely consumed
  4. additionby slowly adding dilute aqueous HCl (3%, ˜25 mL)
  5. additionThe contents of the flask are poured into a separatory funnel
  6. additioncontaining EtOAc (60 mL)
  7. customThe layers are separated
  8. extractionThe aqueous layer is extracted with EtOAc (30 mL)
  9. washThe combined organic extracts are washed with water (35 mL) and brine (35 mL)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-9d99c06df8c34af2b6286a0d8ddc098c
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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