Reaction #550890

Reaction equation

alpha-(aminomethyl)-3,4-dimethoxybenzeneacetic acid ethyl ester hydrochloride

3,4-dimethoxyphenyl acetic acid chloride

thionyl chloride

3,4-dimethoxyphenyl acetic acid

sodium hydroxide

→

2-(3,4-dimethoxyphenyl)-3-{{[(3,4-dimethoxyphenyl)methyl]carbonyl}amino}propanoic acid ethyl ester

Solvents

water

methylene chloride

toluene

methylene chloride

Conditions

Workup

1. 1
   Temperaturewas cooled to 0°
2. 2
   Otherevaporation to dryness]
3. 3
   workup.ADDITIONwas added concurrently with 4N sodium hydroxide maintaining a pH of 7.0-8.0
4. 4
   workup.ADDITIONUpon completion of the acid chloride addition
5. 5
   Temperaturethe pH was maintained at 9.0 for 1 hour
6. 6
   OtherThe layers were separated
7. 7
   Extractionthe aqueous layer extracted once with methylene chloride
8. 8
   WashThe combined organic layers were washed once with excess saturated sodium bicarbonate solution
9. 9
   Dryingdried over sodium sulfate
10. 10
    Otherevaporated in vacuo

Procedure

A mixture of 289 g of alpha-(aminomethyl)-3,4-dimethoxybenzeneacetic acid ethyl ester hydrochloride, 1000 ml of methylene chloride and 1000 ml of water was cooled to 0° and adjusted to pH 9.0 with 4N sodium hydroxide. A solution of 1000 ml of methylene chloride and 3,4-dimethoxyphenyl acetic acid chloride [previously prepared by the action of 400 ml of thionyl chloride on 215 g of 3,4-dimethoxyphenyl acetic acid in 500 ml of toluene at 50° for 1 hour and evaporation to dryness] was added concurrently with 4N sodium hydroxide maintaining a pH of 7.0-8.0. Upon completion of the acid chloride addition, the pH was maintained at 9.0 for 1 hour followed by acidification to pH 1.0 with 6N hydrochloric acid. The layers were separated and the aqueous layer extracted once with methylene chloride. The combined organic layers were washed once with excess saturated sodium bicarbonate solution, dried over sodium sulfate and evaporated in vacuo to give 430 g of 2-(3,4-dimethoxyphenyl)-3-{{[(3,4-dimethoxyphenyl)methyl]carbonyl}amino}propanoic acid ethyl ester as an oil.

Source