Methanol → HCID 68157608, compound

HRID 537558Notes

Reaction equation

HRID 537558 reaction equation
[F:1][C:2]1([F:34])[CH2:5][CH:4]([CH:6]([NH:18][C:19]2[CH:20]=[N:21][C:22]([N:25]3[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[N:27]=[CH:26]3)=[CH:23][CH:24]=2)[C:7]2[CH:17]=[CH:16][C:10]([C:11]([O:13]CC)=[O:12])=[CH:9][CH:8]=2)[CH2:3]1.O1CCCC1.CO.[OH-].[Na+]>C(Cl)Cl>[F:34][C:2]1([F:1])[CH2:5][CH:4]([CH:6]([NH:18][C:19]2[CH:20]=[N:21][C:22]([N:25]3[CH:29]=[C:28]([C:30]([F:31])([F:32])[F:33])[N:27]=[CH:26]3)=[CH:23][CH:24]=2)[C:7]2[CH:17]=[CH:16][C:10]([C:11]([OH:13])=[O:12])=[CH:9][CH:8]=2)[CH2:3]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 14798Sodium Hydroxide3×HCID 68157309HCID 68157309, compound

Product 1

HCID 68157608HCID 68157608, compoundYield 72.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a flask containing impure ethyl 4-((3,3-difluorocyclobutyl)(6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridin-3-ylamino)methyl)benzoate (35.0 mg, 0.073 mmol) was added tetrahydrofuran (0.180 mL), methanol (0.180 mL), and 1 N sodium hydroxide (0.180 mL, 0.180 mmol) was then added. After 2 h, another 5 equiv. of aqueous sodium hydroxide was added. The suspension was stirred at room temperature for 18 hours. Another 5 equiv. of aqueous sodium hydroxide was added and the reaction was heated to 50° C. After 2 h, the reaction was quenched with 1 N hydrochloric acid to pH 3 and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give crude material. The crude material was azeotrophed three times with methylene chloride and then dried in vacuo for 18 h to provide crude 4-((3,3-difluorocyclobutyl)(6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridin-3-ylamino)methyl)benzoic acid (24.0 mg). MS (M+1): 453.2.

Workup

  1. additionwas then added
  2. temperaturethe reaction was heated to 50° C
  3. waitAfter 2 h
  4. customthe reaction was quenched with 1 N hydrochloric acid to pH 3
  5. extractionextracted three times with ethyl acetate
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give crude material
  10. customdried in vacuo for 18 h

Sources & evidence

ORD record
ord-ec12c87faf7d4e52acb95d532d9d7d72
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

Loading…