Reaction #40282

Reaction equation

2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-propionamide

hydrochloric acid

→

2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1 (S),2-dihydroxy-ethyl)-pyrazin-2-yl]-propionamide

Yield 88.0%

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   OtherThe resulting milky reaction mixture
2. 2
   Otherthe milky reaction mixture
3. 3
   workup.WAITThe stirring was continued at 25° C. for 16 h
4. 4
   ConcentrationThe reaction was concentrated in vacuo
5. 5
   Extractionthe residue was extracted with methylene chloride (1×100 mL
6. 6
   ExtractionEach organic extract
7. 7
   Washwas washed with a saturated aqueous sodium bicarbonate solution (50 mL)
8. 8
   DryingThe combined organic layers were dried over sodium sulfate
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated in vacuo

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-propionamide (8.85 g, 17.4 mmol) in tetrahydrofuran (50 mL) was treated with a 1N aqueous hydrochloric acid solution (50 mL). The resulting milky reaction mixture was stirred at 25° C., and within 15 min, the milky reaction mixture became clear. The stirring was continued at 25° C. for 16 h. The reaction was concentrated in vacuo, and the residue was extracted with methylene chloride (1×100 mL then 2×50 mL). Each organic extract was washed with a saturated aqueous sodium bicarbonate solution (50 mL) and a saturated aqueous sodium chloride solution (50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40 L, Silica, 1/1 ethyl acetate/hexanes then 100% ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1 (S),2-dihydroxy-ethyl)-pyrazin-2-yl]-propionamide (7.15 g, 88%) as a colorless foam. (ES)+-HRMS m/e calcd for C21H26ClN3O5S (M+H)+ 468.1355, found 468.1360.

Source