Tetrahydrofuran → 6-Cyclopropylmethoxy-1H-indole-2-carboxylic acid methyl ester

HRID 1171215Notes

Reaction equation

HRID 1171215 reaction equation
O1[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:6][O:7][C:8]([C:10]1[NH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[C:14]([OH:19])[CH:13]=2)=[O:9].[OH-].[Na+].C1(CBr)CC1>O.CN(C)C=O>[CH3:6][O:7][C:8]([C:10]1[NH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[C:14]([O:19][CH2:2][CH:3]1[CH2:5][CH2:4]1)[CH:13]=2)=[O:9]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 81503BromomethylcyclopropaneHCID 10535709methyl 6-hydroxy-1H-indole-2-carboxylate

Product 1

HCID 576082536-Cyclopropylmethoxy-1H-indole-2-carboxylic acid methyl esterYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a tetrahydrofuran (8 mL) solution of 6-hydroxy-1H-indole-2-carboxylic acid methyl ester (395 mg, 2.07 mmol) described in Production Example 73-1-1 was added 5 N aqueous sodium hydroxide solution (414 μL, 2.07 mmol), which was concentrated under a reduced pressure. To an N,N-dimethylformamide (8 mL) solution of the residue was added cyclopropylmethyl bromide (241 μL, 2.48 mmol) at room temperature followed by stirring at room temperature for 12 hours. Moreover, after stirring at 50° C. for 4 hours, water was added to the reaction solution at room temperature followed by extraction with ethyl acetate. The organic layer was washed with water and sat. NaCl followed by drying over anhydrous magnesium sulfate and filtering. The filtrate was concentrated under a reduced pressure and the residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1) to obtain the title compound (297 mg, 59%) as a white solid.

Workup

  1. concentrationwas concentrated under a reduced pressure
  2. stirringMoreover, after stirring at 50° C. for 4 hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with water and sat. NaCl
  5. dry with materialby drying over anhydrous magnesium sulfate
  6. filtrationfiltering
  7. concentrationThe filtrate was concentrated under a reduced pressure
  8. customthe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-ffe864bf97394553b56a98d4d83b9aa3
Source dataset
uspto-grants-2010_11
Patent number
US07829585B2

Reaction notes

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