Hydrochloric Acid → HCID 57748359, compound

HRID 906203Notes

Reaction equation

HRID 906203 reaction equation
[C@H:1]([NH:5][C:6]1[C:7]([C:20]([NH2:22])=[O:21])=[CH:8][C:9]([C:16]([F:19])([F:18])[F:17])=[C:10]([CH:15]=1)[C:11]([O:13]C)=[O:12])([CH2:3][CH3:4])[CH3:2].[OH-].[Na+].ClCCl.Cl>CO>[NH2:22][C:20]([C:7]1[C:6]([NH:5][C@H:1]([CH3:2])[CH2:3][CH3:4])=[CH:15][C:10]([C:11]([OH:13])=[O:12])=[C:9]([C:16]([F:17])([F:18])[F:19])[CH:8]=1)=[O:21]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6344Dichloromethane2×HCID 14798Sodium Hydroxide3×HCID 67402485HCID 67402485, compound

Product 1

HCID 57748359HCID 57748359, compoundYield 89.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
45 °C

Procedure

(R)-Methyl 5-(sec-butylamino)-4-cyano-2-(trifluoromethyl)benzoate (45 mg, 0.150 mmol) was dissolved in DMSO (1 mL) and was treated with 30% aqueous hydrogen peroxide (0.05 mL) and potassium carbonate (6 mg, 0.043 mmol) at ambient temperature for 2 h. The reaction mixture was partitioned between ethyl acetate and water. The aqueous portion was extracted with ethyl acetate. The combined organic portion was dried over sodium sulfate, then filtered and concentrated to afford a yellow oil which was purified by column chromatography (silica gel, 10-40% ethyl acetate in hexanes) to afford (R)-methyl 5-(sec-butylamino)-4-aminocarbonyl-2-(trifluoromethyl)benzoate (27 mg, 0.085 mmol, 57% yield). (R)-M ethyl 5-(sec-butylamino)-4-aminocarbonyl-2-(trifluoromethyl)benzoate (27 mg, 0.085 mmol) was suspended in methanol (1 mL) and was treated with 1 M sodium hydroxide (0.2 mL, 0.2 mmol) at 45° C. for 1 h. Dichloromethane (0.5 mL) and 1M sodium hydroxide (0.2 mL, 0.2 mmol) was added and the mixture was stirred at 45° C. for a further 1.5 h. Dichloromethane (0.5 mL) and 1M sodium hydroxide (0.2 mL, 0.2 mmol) were added, and the mixture was stirred at 45° C. for a further 1 h and then at ambient temperature for 15 h. The reaction mixture was concentrated to afford an aqueous residue that was cooled in an ice bath, was acidified with 1N hydrochloric acid to pH ˜2, then extracted with ethyl acetate (2×). The organic portion was dried over sodium sulfate, then filtered and concentrated to provide 4-(aminocarbonyl)-5-{[(1R)-1-methylpropyl]amino}-2-(trifluoromethyl)benzoic acid (23 mg, 0.076 mmol, 89% yield). MS (EI) for C13H15F3N2O3: 305 (MH+).

Workup

  1. stirringthe mixture was stirred at 45° C. for a further 1 h
  2. waitat ambient temperature for 15 h
  3. concentrationThe reaction mixture was concentrated
  4. customto afford an aqueous residue that
  5. temperaturewas cooled in an ice bath
  6. extractionextracted with ethyl acetate (2×)
  7. dry with materialThe organic portion was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-22079a5de4d94906b52a369b03e0148f
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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