2,4,5-Trichlorophenol → HCID 70073156, compound

Temperature

0 °C

3.7 g (17.2 mmole) of ethoxycarbonyl-3-cyclobutyl-D-alanine (Example 1, Step D) is dissolved in 60 ml of tetrahydrofuran, cooled to 0° C., then 4.85 g (24.5 mmol) of 2,4,5-trichlorophenol and 5.06 g (24.5 mmol) of dicyclohexyl-carbodiimide are added. The reaction mixture is stirred at room temperature for 2 hours, filtered from the separated dicyclohexylurea and washed with tetrahydrofuran. The filtrate and the washings are pooled and evaporated at a pressure of 2.0-2.5 kPa. The residue is dissolved in 25 ml of diethyl ether-petroleum ether mixture (1:1), the insoluble dicyclohexylurea is filtered off and the filtrate is evaporated again [the filtered dicyclohexylurea amounts to 4.9 g (89%) and 0.6 g (11%), respectively]. The oily 2,4,5-trichlorophenyl ethoxycarbonyl-3-cyclobutyl-D-alaninate is dissolved in 40 ml of pyridine and 2.12 g (18.4 mmol) of finely pulverised L-proline is added together with 3.43 ml (24.6 mmol) of triethyl amine. The reaction mixture is stirred at room temperature for 3 hours, then evaporated at a pressure of 2.0-2.5 kPa. The residue is distributed between 50 ml of ethyl acetate and 50 ml of 1M HCl. The organic phase is washed first with 10 ml of 1M HCl then with 2×10 ml of water and is extracted with 3×100 ml of 5% NaHCO3. The pooled hydrocarbonate extracts are acidified to pH3 with 6M HCl and extracted with 3×20 ml of diethyl ether. The ethereal extracts are pooled, washed acid-free with water, dried over anhydrous sodium sulphate and evaporated to dryness.

1. filtrationfiltered from the separated dicyclohexylurea
2. washwashed with tetrahydrofuran
3. customevaporated at a pressure of 2.0-2.5 kPa
4. dissolutionThe residue is dissolved in 25 ml of diethyl ether-petroleum ether mixture (1:1)
5. filtrationthe insoluble dicyclohexylurea is filtered off
6. customthe filtrate is evaporated again [the filtered dicyclohexylurea
7. dissolutionThe oily 2,4,5-trichlorophenyl ethoxycarbonyl-3-cyclobutyl-D-alaninate is dissolved in 40 ml of pyridine
8. stirringThe reaction mixture is stirred at room temperature for 3 hours
9. customevaporated at a pressure of 2.0-2.5 kPa
10. washThe organic phase is washed first with 10 ml of 1M HCl
11. extractionwith 2×10 ml of water and is extracted with 3×100 ml of 5% NaHCO3
12. extractionextracted with 3×20 ml of diethyl ether
13. washwashed acid-free with water
14. dry with materialdried over anhydrous sodium sulphate
15. customevaporated to dryness

ORD record

ord-c0b6c6b94cbb42448ef65a459d707c23

Source dataset

uspto-grants-2001_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06235707B1