反应详情

温度

-5 °C

A suspension of (S)-3-methyl-2-((2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl)-amino)-butyric acid (17.6 g; 50.0 mmol) in 1,2-dimethoxyethan (116 g) is cooled to −5° C., and valeroyl-chloride (9.9 ml; 80 mmol) is added, followed by slow addition of pyridine (6.0 ml; 75 mmol) diluted with 1,2-dimethoxyethane (60 ml). [1] After completion of the reaction, the reaction mixture is quenched with methanol (18 ml). Finally water (50 ml) is added at room temperature, and after stirring for 1 h, the mixture is adjusted to pH 7.5 by addition of aqueous sodium carbonate solution 10% (˜116 ml, 120 mmol) at 0° C. The organic solvents are stripped off at 50° C. in vacuo. Ethylacetate (125 ml) is added to the remaining aqueous concentrate, and the two-phase system is adjusted to pH 2 at 0-5° C. by addition of 2.0 M HCl (˜98 ml). The organic phase is separated and concentrated at 45° C. in vacuo (water is azeotropically removed). The crystallization of the product is initiated at 45° C. and—after addition of cyclohexan (102 ml)—completed by cooling to −5° C. The solid is collected by filtration, and after drying at 50° C., (S)-3-methyl-2-{pentanoyl-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-amino}-butyric acid is received as a white powder.

1. customthe reaction mixture is quenched with methanol (18 ml)
2. additionFinally water (50 ml) is added at room temperature
3. customare stripped off at 50° C. in vacuo
4. customThe organic phase is separated
5. concentrationconcentrated at 45° C. in vacuo (water
6. customis azeotropically removed)
7. customThe crystallization of the product
8. customis initiated at 45° C.
9. addition—after addition of cyclohexan (102 ml)
10. temperatureby cooling to −5° C
11. filtrationThe solid is collected by filtration
12. customafter drying at 50° C.