Réaction #86785

Équation de réaction

(R)-1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-ol

MgCl2

1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-one

NAD

→

1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-ol

Rendement 99.6%

Solvants

ethyl acetate

butyl acetate

2-propanol

glycerol

Conditions de réaction

Traitement

1. 1
   AutreAfter being separated
2. 2
   Autrethe organic layer thus formed
3. 3
   Lavagewas washed with 10% brine (3×500 mL)
4. 4
   AutreThe organic layer thus formed
5. 5
   Séchagewas dried over magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   workup.DISTILLATIONthe filtrate was distilled under reduced pressure

Mode opératoire

50 ml of the enzyme solution 2 containing the oxidoreductase SEQ NO: 2 were added to a mixture of 250 ml of a buffer (100 mM TEA, pH 8, 1 mM MgCl2, 10% glycerol), 50 g (225 mmol) of 1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-one (2N ketone), 4 mg NAD, 300 ml of 2-propanol and 150 mL of butyl acetate. The reaction mixture was stirred at room temperature. After 48 hours more than 98% of 2N ketone was reduced to corresponding (R)-1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-ol (R-2N alcohol) with >99% ee values. To this resulting mixture, 500 mL of ethyl acetate was added. After being separated, the organic layer thus formed was washed with 10% brine (3×500 mL). The organic layer thus formed was dried over magnesium sulfate and filtered and the filtrate was distilled under reduced pressure to give 50.4 g (224 mmol) of 1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-ol (R-2N alcohol, optical purity 99.9%) as an oily residue. To this resulting crude product, 450 mL of tetrahydrofuran was added. After cooling to −15° C., 38 g (267 mmol) of chlorosulfonyl isocyanate was slowly added and stirred at −10° C. for 2 h. The slow addition of water induced termination of the reaction. The resulting solution was concentrated under reduced pressure until about 300 mL of the solvent was removed. The concentrate was diluted with 600 mL of ethyl acetate and washed with 10% brine (3×500 mL). The organic layer was concentrated under reduced pressure and the concentrate was dissolved in isopropanol (90 mL) to which heptane (180 mL) was slowly added, leading to the completion of crystallization. The precipitate thus obtained was filtered and washed to afford 51.8 g (194 mmol) of carbamic acid (R)-1-(2-chiorophenyl)-2-(tetrazol-2-yl)ethyl ester (optical purity 99.9%).

Source