Diethyl Ether → (S)-4-[4-[[7-(Aminosulfonyl)-6-chloro-3,4-dihydro-1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl]methyl]phenoxy]-1-[(S)-3-mercapto-2-methyl-1-oxopropyl]-L-proline

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Reaction Steps

The product from Example 1 (0.3 g., 0.4 mmole) is dissolved in 50 ml. of argon purged sodium hydroxide (2.5%) and stirred at 25° for 3 hours. The solution is acidified with 10% potassium bisulfate and extracted with ethyl acetate. The organics are dried (Na2SO4) and evaporated. Trituration with ether gives a solid. Chromatography on 50 g. of LH-20 in methanol and pooling and evaporation of the product containing fractions gives a glass. Trituration with ether gives 0.2 g. of (S)-4-[[7-(aminosulfonyl)-6-chloro-3,4-dihydro-1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl]methyl]phenoxy]-1-[(S)-3-mercapto-2-methyl-1-oxopropyl]-L-proline as a white crystalline solid; m.p. 175°-185°; [α]D =-22° (c=0.1%, methanol). TLC (silica, methylene chloride:methanol:acetic acid; 8:1:1) Rf =0.32.

Provenance & Evidence