Reaction #74193

Reaction equation

water

4′-{5-[((S)-2-acetylsulfanyl-4-methylpentanoylamino)methyl]-2-ethoxy-4-ethylimidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic acid

DTT

AcOH

→

compound

Yield 56.9%

4′-{2-Ethoxy-4-ethyl-5-[((S)-2-mercapto-4-methylpentanoylamino)methyl]imidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic Acid

Yield 56.9%

Solvents

MeOH

Conditions

Workup

1. 1
   OtherThe resulting solution was degassed with nitrogen (3 times)
2. 2
   workup.ADDITIONNaOMe (25% in MeOH, 1.7 mL) was added
3. 3
   Otherto quench
4. 4
   Otherthe reaction at 0° C
5. 5
   TemperatureThe mixture was warmed to 20° C
6. 6
   workup.STIRRINGThe mixture was stirred at 20° C. for 3 hours
7. 7
   workup.STIRRINGstirred at 4° C. for 1 hour
8. 8
   Otheruntil precipitates
9. 9
   Otherwere formed
10. 10
    FiltrationThe solids were filtered
11. 11
    Washwashed with MeOH/H2O (2:1; 30 mL)
12. 12
    Otherdried under nitrogen at 20° C. for 48 hours

Procedure

Crystalline 4′-{5-[((S)-2-acetylsulfanyl-4-methylpentanoylamino)methyl]-2-ethoxy-4-ethylimidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic acid (2.3 g, 4 mmol, 1 eq.) and DTT (62 mg, 0.4 mmol, 0.1 eq.) was dissolved in MeOH (30 mL). The resulting solution was degassed with nitrogen (3 times) and cooled at 0° C. NaOMe (25% in MeOH, 1.7 mL) was added and the mixture was stirred at 0° C. for 30 minutes. AcOH (3 g, 50 mmol, 4 eq.) was added to quench the reaction at 0° C. The mixture was warmed to 20° C. Deionized water (10 mL) was added slowly. The mixture was stirred at 20° C. for 3 hours and then stirred at 4° C. for 1 hour until precipitates were formed. The solids were filtered and washed with MeOH/H2O (2:1; 30 mL), then dried under nitrogen at 20° C. for 48 hours to yield the title crystalline compound (1.2 g).

Source