p-Toluenesulfonic acid → HCID 13823434, compound

Participants

Reaction Steps

A 10-gallon extractor was charged with 12.0 L of 3N Na2CO3, 575 g (1.02 mole) of (2S,3S)-3-[(2-amino-1-naphthalenyl)thio]-2-hydroxy-3-(4-methoxyphenyl) propanoic acid (1R,2S)-2-phenylcyclohexyl ester hydrochloride and 8.0 L of methylene chloride. The aqueous layer was successively extracted with an additional 4L+2L=6.0 L of methylene chloride. The combined organic layers were dried by filtration through a pad of anhydrous potassium carbonate and evaporated in vacuo to afford the free base which was taken up in 11.5 L of xylene. Then 16 g of p-toluene sulfonic acid.monohydrate was added and this mixture was stirred at reflux under argon for 16 hours (overnight). After cooling, the product was collected by filtration, washed with 500 mL of ethyl acetate, followed by 3×500 mL =1.5 L of ether and air dried overnight to afford 318 g (89%) of (2 S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-naphtho-[1,2-b][1,4]thiazepin-4(5H)-one as colorless needles, m.p. 235-238° decomposition, [α]D20 =+24.87°(c=0.4; acetone).

Provenance & Evidence