Hydrochloric Acid → 2-Amino-2-(4-methoxyphenyl)ethan-1-ol

Participants

Reaction Conditions

Reaction Steps

A mixture of 3.4 g of tert-butyl 1-(4-methoxyphenyl)-2-hydroxyethylcarbamate in 32 cm3 of methanol containing 10% by mass of anhydrous hydrogen chloride is stirred for 1 hour at a temperature in the region of 20° C. The reaction medium is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue is taken up in 9 cm3 of aqueous 5% sodium hydrogen carbonate solution and the mixture is then extracted with 3 times 30 cm3 of dichloromethane. The aqueous phase is concentrated as above and the white solid obtained is then taken up in 17 cm3 of aqueous 1N sodium hydroxide solution. The precipitate is extracted with 3 times 30 cm3 of dichloromethane. The combined organic extracts are evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The white solid obtained is dried under reduced pressure (10 Pa) at a temperature in the region of 40° C. 1.3 g of 2-amino-2-(4-methoxyphenyl)-1-ethanol are obtained in the form of a white solid melting at 96° C. tert-Butyl 1-(4-methoxyphenyl)-2-hydroxyethylcarbamate: 2.24 g of lithium chloride are added to a solution of 7.8 g of methyl N-Boc-(4-methoxyphenyl)glycinate in 35 cm3 of tetrahydrofuran cooled to a temperature of 0° C., followed by portionwise addition of 1.99 g of sodium borohydride and finally 74 cm3 of ethanol. The temperature is allowed to return to about 20° C. and the reaction is then completed by stirring the mixture for 18 hours at this same temperature. The medium is re-cooled to about 5° C. and a sufficient amount of aqueous 1M sodium hydrogen sulfate solution to give a pH in the region of 2 is then added thereto. The mixture is stirred for 3 hours and is then evaporated under reduced pressure (5 kPa) at a temperature in the region of 50° C. 60 cm3 of dichloromethane and 30 cm3 of aqueous 1M sodium hydrogen sulfate solution are added to the residue obtained. After stirring the mixture and then separating out the organic phase after settling of the phases has taken place, the aqueous phase is extracted with twice 30 cm3 of dichloromethane. The combined organic extracts are dried over sodium sulfate and concentrated as above. A white solid is obtained, which is taken up in 30 cm3 of cyclohexane and filtered. The crystals are dried under reduced pressure (10 Pa) at a temperature in the region of 60° C. 3.47 g of tert-butyl 1-(4-methoxyphenyl)-2-hydroxyethylcarbamate are obtained in the form of a white solid melting at 130° C.

Provenance & Evidence