Trimethylamine → (S)-4-((2,4-dichlorophenoxyacetyl)amino)-5-fluoropentanoic acid, methyl ester

0.70 g of 2,4-dichlorophenoxyacetic acid, 0.59 g of 4 and 0.44 ml of trimethylamine were mixed with 75 ml of methylene chloride, and the mixture was stirred at room temperature for 30 minutes. Then, 0.65 g of N,N'-dicyclohexylcarbodiimide was added and the mixture was stirred at room temperature overnight. Several drops of glacial acetic acid were added and the mixture was filtered. The filtrate was washed successively with water, 1N hydrochloric acid, and half-saturated aqueous sodium bicarbonate solution, dried (Na2SO4) and stripped of solvent. The residue was triturated with ethyl acetate, the mixture was filtered and the solvent was evaporated from the filtrate under reduced pressure. The solid residue was triturated with hexane, the mixture was filtered and the solvent was evaporated from the filtrate. The solid residue was chromatographed over silica gel, first with a 1:3 v:v mixture of ethyl acetate and hexane as eluent, then with a 1:1 v:v mixture of ethyl acetate and hexane as eluent. On workup, 16 was obtained, as a white solid.

1. stirringthe mixture was stirred at room temperature overnight
2. filtrationthe mixture was filtered
3. washThe filtrate was washed successively with water, 1N hydrochloric acid, and half-saturated aqueous sodium bicarbonate solution
4. dry with materialdried (Na2SO4)
5. customThe residue was triturated with ethyl acetate
6. filtrationthe mixture was filtered
7. customthe solvent was evaporated from the filtrate under reduced pressure
8. customThe solid residue was triturated with hexane
9. filtrationthe mixture was filtered
10. customthe solvent was evaporated from the filtrate
11. customThe solid residue was chromatographed over silica gel, first with a 1:3 v
12. additionv mixture of ethyl acetate and hexane as eluent
13. additionwith a 1:1 v:v mixture of ethyl acetate and hexane as eluent
14. customOn workup, 16 was obtained, as a white solid

ORDレコード

ord-5a6c45bef63a4c6ba8582ea58a66896b

出典データセット

uspto-grants-1985_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US04528028