Reaction #47273

Reaction equation

sodium hydroxide

2-chlorophenol

potassium t-butoxide

ethyl 2-butynoate

→

(E)-3-(2-chloro-phenoxy)-but-2-enoic acid ethyl ester

Yield 104.3%

Solvents

methyl t-butyl ether

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   TemperatureThe solution was warmed to 22° C.
2. 2
   workup.ADDITIONwas added in one portion
3. 3
   TemperatureThe resulting mixture was warmed to 40° C.
4. 4
   workup.STIRRINGThe mixture was stirred
5. 5
   Otherseparated
6. 6
   Washthe organic phase washed with an 1N aqueous sodium hydroxide solution (14 L)
7. 7
   Extractionextracted with methyl t-butyl ether (10 L)
8. 8
   WashThe organic layer was washed with an 1N aqueous sodium hydroxide solution (7 L)
9. 9
   WashThe combined organic phases were washed with a 20% sodium chloride solution (14 L)
10. 10
    OtherThe solution was evaporated

Procedure

To a solution of 2-chlorophenol (3186 g, 24.78 mol) in tetrahydrofuran (14000 mL) at 12° C. was added a 20% potassium t-butoxide solution in tetrahydrofuran (8150 mL, 13.48 mol) over 45 min maintaining an internal temperature between 12-17° C. The solution was warmed to 22° C. and stirred for 1 h before ethyl 2-butynoate (1400 g, 12.48 mol) was added in one portion. The resulting mixture was warmed to 40° C., and stirred for 19.75 h. The reaction mixture was transferred to an extractor and was diluted with methyl t-butyl ether (21 L) and an aqueous 1N aqueous sodium hydroxide solution (14 L). The mixture was stirred and separated and the organic phase washed with an 1N aqueous sodium hydroxide solution (14 L). The aqueous phases were combined and extracted with methyl t-butyl ether (10 L). The organic layer was washed with an 1N aqueous sodium hydroxide solution (7 L). The combined organic phases were washed with a 20% sodium chloride solution (14 L). The solution was evaporated to give (E)-3-(2-chloro-phenoxy)-but-2-enoic acid ethyl ester (96.9% pure by HPLC, 3134 g, 101%) as a light yellow oil.

Source