Methanol → HCID 59314105, compound

HRID 1047908Notes

Reaction equation

HRID 1047908 reaction equation
C([O:3][C:4]([C:6]1([NH:15][C:16]([C:18]2[C:19]([O:24][CH2:25][CH3:26])=[N:20][CH:21]=[CH:22][CH:23]=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>[CH2:25]([O:24][C:19]1[C:18]([C:16]([NH:15][C:6]2([C:4]([OH:5])=[O:3])[CH2:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH2:7]2)=[O:17])=[CH:23][CH:22]=[CH:21][N:20]=1)[CH3:26]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 312751,4-DioxaneHCID 59314110HCID 59314110, compound

Product 1

HCID 59314105HCID 59314105, compoundYield 140.4%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

A 100 mL flask containing 2-[(2-ethoxy-pyridine-3-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester ([313], 340 mg, 0.96 mmol) is charged with 1,4-dioxane (4 mL) and MeOH (4 mL). A stirring bar is added and stirring is initiated. After dissolution, water (2 mL) is added followed by the LiOH monohydrate (102 mg, 2.42 mmol). After 13 days, tlc analysis (silica, 10% MeOH/DCM) indicates that the starting material is completely consumed. The contents of the flask are diluted with iPrOH (30 mL). Dowex Highly Acidic Ion Exchange Resin (2 g) is added. The reaction flask is capped and allowed to stir at ambient temperature. After 18 h, additional iPrOH (35 mL) is added to the reaction flask. The contents of the reaction flask are filtered through a pad of Celite and concentrated under reduced pressure by pumping to constant weight to yield 0.44 g of white solid. This material is dissolved in a mixture of DCM (10 mL) and iPrOH (3 mL). Celite (15 g) is added to the flask. The solvent is removed under reduced pressure. The remaining material is transferred to a 40 mL plastic syringe that is fitted with a fritted disk. The syringe is fitted onto an ISCO Companion which had a 40 g column (silica). The following gradient is applied. 1% IPrOH/DCM for 4 column volumes. Then a linear gradient to 50% iPrOH/DCM over 10 column volumes. Hold at 50% iPrOH/DCM for 2 Column Volumes. 14 mL fractions are collected. Fractions 39-41 are combined and evaporated by pumping to constant weight to yield white solid (0.28 g, 89%).

Workup

  1. additionA stirring bar is added
  2. additionis added
  3. customis completely consumed
  4. additionThe contents of the flask are diluted with iPrOH (30 mL)
  5. additionDowex Highly Acidic Ion Exchange Resin (2 g) is added
  6. customThe reaction flask is capped
  7. stirringto stir at ambient temperature
  8. waitAfter 18 h
  9. additionadditional iPrOH (35 mL) is added to the reaction flask
  10. filtrationThe contents of the reaction flask are filtered through a pad of Celite
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c1e9fd4273b845e281e9cbdb7d06d74c
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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