Dicyclohexylamine → Benzyl 2-[[2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetyl]amino]acetate

In 380 ml of a chloroform/methylene chloride/ethyl acetate (7:5:1 by volume) mixed solvent were dissolved 7.13 g (20 mmol) of t-butyloxycarbonylglycine.dicyclohexylamine and 5.18 g (20 mmol) of glycylglycine benzyl ester hydrochloride obtained in Example 1. To this solution, 50 ml of a chloroform solution containing 4.22 g (20 mmol) of EDAC were added at -5° C. with stirring. The resulting mixture was stirred for 24 hours. The resulting chloroform solution was successively washed twice with a 10% by weight aqueous citric acid solution, then twice with water, then twice with a 4% by weight aqueous sodium hydrogen carbonate solution and finally twice with water. Thereafter, the organic phase was dried over anhydrous sodium sulfate. The solvent was then completely removed in vacuo to obtain a white oily material. This was crystallized from hexane to obtain 6.52 g (yield: 86%) of t-butyloxycarbonylglycylglycylglycine benzyl ester as a white solid. This benzyl ester was dispersed, to which 130 ml of 4N HCl/ethyl acetate were added. The mixture was stirred for 4 hours and then the solvent was removed in vacuo to obtain white precipitates. The precipitates were washed well with diethyl ether to obtain 4.63 g (yield: 85%) of glycylglycylglycine benzyl ester hydrochloride as a white solid having the following physical properties:

1. additionwere added at -5° C.
2. stirringThe resulting mixture was stirred for 24 hours
3. washThe resulting chloroform solution was successively washed twice with a 10% by weight aqueous citric acid solution
4. dry with materialThereafter, the organic phase was dried over anhydrous sodium sulfate
5. customThe solvent was then completely removed in vacuo
6. customto obtain a white oily material
7. customThis was crystallized from hexane

ORDレコード

ord-7cebb6f6c8154f31b90ba6b4c8ab905d

出典データセット

uspto-grants-1999_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05876748