Reaktion #308686

Reaktionsgleichung

1-chloroethyl cyclohexyl carbonate

potassium iodide

potassium carbonate

(R)-7-[3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid

(R)-7-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid

2a

(R)-7-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid

→

(R)-7-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid (1-cyclohexyloxycarbonyloxy)-ethyl ester

Ausbeute 69.4%

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.DISSOLUTIONwas dissolved
2. 2
   workup.ADDITIONUpon completion of the addition
3. 3
   Sonstigethe reaction tube was sealed up
4. 4
   SonstigeThe reaction mixture was reacted at 65° C. in an oil bath for 2 hours
5. 5
   Sonstigethe oil bath was removed
6. 6
   workup.ADDITION40 mL of water was added to the reaction tube
7. 7
   ExtraktionThe reaction mixture was extracted with ethyl acetate (30 mL×3)
8. 8
   WaschenThe combined organic phase was washed with 30 mL of water and 30 mL of saturated brine successively
9. 9
   TrocknenThe combined organic phase was dried over anhydrous magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated under reduced pressure
12. 12
    SonstigeThe resulting residue was purified by silica gel column chromatography

Vorschrift

(R)-7-[3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid 2a (0.275 g, 0.5 mmol) and 4 mL of N,N-dimethylformamide were added to the reaction tube. After stirring until 2a was dissolved, 1-chloroethyl cyclohexyl carbonate (0.124 g, 0.6 mmol), potassium iodide (0.0415 g, 0.25 mmol) and potassium carbonate (0.083 g, 0.6 mmol) were then added to the solution successively. Upon completion of the addition, the reaction tube was sealed up. The reaction mixture was reacted at 65° C. in an oil bath for 2 hours and monitored by thin layer chromatography until the disappearance of the starting materials, and then the oil bath was removed. After cooling to room temperature, 40 mL of water was added to the reaction tube. The reaction mixture was extracted with ethyl acetate (30 mL×3). The combined organic phase was washed with 30 mL of water and 30 mL of saturated brine successively. The combined organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (R)-7-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid (1-cyclohexyloxycarbonyloxy)-ethyl ester 38a (0.25 g, yield 69.4%) as a white solid.

Quelle