Reaction #321423

Reaction equation

ethyl acetimidate hydrochloride

hydrochloric acid

product

(R)-4-(3-aminomethyl-1,2,4-oxadiazol-5-yl)-16-[dimethyl-(1,1,2-trimethyl-propyl)silanyloxy]-14-methoxy-13-methyl-6-thioxo-1,3,4,5,6,7,8,9,10,12-decahydro-11,2,5-benzoxathiaazacyclotetradecin-12-one

sodium phosphate

sodium hydroxide

→

(4R)-N-[5-(16-hydroxy-14-methoxy-13-methyl-12-oxo-6-thioxo-1,3,4,5,6,7,8,9,10,12-decahydro-11,2,5-benzoxathiaazacyclotetradecin-4-yl)-1,2,4-oxadiazol-3-ylmethyl]-acetimidamide

Yield 24.0%

Conditions

Workup

1. 1
   Temperaturethe pH of the reaction mixture being maintained at 8.5
2. 2
   Extractionextracted with ethyl acetate
3. 3
   ConcentrationThe aqueous phase was concentrated in vacuo
4. 4
   Otherchromatographed on MCI-Gel CHP20P (Mitsubishi Chemical Industries, Ltd.)

Procedure

The pH of a suspension of 20 mg of the product of Example 130 in 3 ml of 0.05M pH7 sodium phosphate buffer was adjusted to 8.5 by the addition of 0.1N sodium hydroxide. Over 3 h, 74 mg of ethyl acetimidate hydrochloride were added in small portions, the pH of the reaction mixture being maintained at 8.5. The mixture was set to pH 7 by addition of 1N hydrochloric acid and then extracted with ethyl acetate. The aqueous phase was concentrated in vacuo and chromatographed on MCI-Gel CHP20P (Mitsubishi Chemical Industries, Ltd.) using at first 1% aqueous acetic acid and then mixtures of 1% aqueous acetic acid with acetonitrile (10:1 to 2:1, v/v). The product-containing fractions were lyophilized to yield 4 mg of (4R)-N-[5-(16-hydroxy-14-methoxy-13-methyl-12-oxo-6-thioxo-1,3,4,5,6,7,8,9,10,12-decahydro-11,2,5-benzoxathiaazacyclotetradecin-4-yl)-1,2,4-oxadiazol-3-ylmethyl]-acetimidamide hydroacetate.

Source