Tetrahydrofuran → 4-({Cyclohexyl[3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridin-2-yl]methyl}amino)benzoic acid

HRID 2091327Notes

Reaction equation

HRID 2091327 reaction equation
[CH:1]1([CH:7]([NH:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29]C)=[O:28])=[CH:25][CH:24]=2)[C:8]2[S:16][C:15]3[C:10](=[N:11][CH:12]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:14]=3)[C:9]=2[CH3:21])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O1CCCC1.[OH-].[Na+]>C(O)C>[CH:1]1([CH:7]([NH:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=2)[C:8]2[S:16][C:15]3[C:10](=[N:11][CH:12]=[C:13]([C:17]([F:18])([F:20])[F:19])[CH:14]=3)[C:9]=2[CH3:21])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 66778478Methyl 4-({cyclohexyl[3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridin-2-yl]methyl}amino)benzoate

Product 1

HCID 667778494-({Cyclohexyl[3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridin-2-yl]methyl}amino)benzoic acidYield 89.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a mixture of methyl 4-({cyclohexyl[3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridin-2-yl]methyl}amino)benzoate (775 mg) synthesized above, tetrahydrofuran (10 mL) and ethanol (10 mL) was added 1N aqueous sodium hydroxide solution (10 mL), and the mixture was stirred for 1 day with heating under reflux, and concentrated under reduced pressure. The residue was dissolved in water (20 mL), and 1N hydrochloric acid (10 mL) was added at 0° C., and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (30-70% ethyl acetate/hexane) to give the title object compound (671 mg, 87%) as a pale-brown solid.

Workup

  1. temperaturewith heating
  2. temperatureunder reflux
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in water (20 mL)
  5. addition1N hydrochloric acid (10 mL) was added at 0° C.
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe extract was washed with saturated brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (30-70% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-14891a8ef3ae4e1c9e9c7d4b82fd7ad6
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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