Reaction #1583896

Reaction equation

Sodium azide

Intermediate ( 8a )

2-Fluoro-4-(6-hydroxymethyl-4-methyl-2-propyl-benzoimidazol-1-ylmethyl)-benzoic acid methyl ester

DIPEA

Methanesulfonyl chloride

→

Intermediate ( 8b )

Yield 81.7%

4-(6-Azidomethyl-4-methyl-2-propylbenzoimidazol-1-ylmethyl)-2-fluorobenzoic acid methyl ester

Yield 81.7%

Solvents

DCM

Conditions

Workup

1. 1
   Concentrationthe mixture was concentrated
2. 2
   workup.DISSOLUTIONthe material redissolved in 40 mL DMF
3. 3
   Temperaturethe mixture was heated at 80° C. for 1 hour
4. 4
   TemperatureThe mixture was then cooled to room temperature
5. 5
   OtherThe solution was partitioned between EtOAc (100 mL) and 50 mL 10% LiCl (aqueous)
6. 6
   ConcentrationThe organic layer was concentrated
7. 7
   Otherflash chromatographed 20-70% EtOAc

Procedure

Intermediate (8a) (2.4 g, 6.5 mmol) was added to 125 mL of DCM followed by DIPEA (4.6 mL, 26.1 mmol) and 4-dimethylaminopyridine (80 mg, 653 μmol). Methanesulfonyl chloride (1.0 mL, 13.1 mmol) was then added at 0° C. and the mixture was warmed to room temperature. After 3 hours, the mixture was concentrated and the material redissolved in 40 mL DMF. Sodium azide (467 mg, 7.2 mmol) was added and the mixture was heated at 80° C. for 1 hour. The mixture was then cooled to room temperature. The solution was partitioned between EtOAc (100 mL) and 50 mL 10% LiCl (aqueous). The organic layer was concentrated and flash chromatographed 20-70% EtOAc:hexanes to yield Intermediate (8b) as a yellow oil (2.1 g). MS m/z: [M+H+] calcd for C21H22FN5O2, 396.2. found 396.0.

Source