반응 #811440

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2-Chloronicotinic acid methyl ester

caesium carbonate

3-methylsulphanyl-phenol

→

title product

2-(3-Methylsulfanyl-phenoxy)-nicotinic acid methyl ester

용매

water

ethyl acetate

—

mixture

toluene 1-methyl-2-pyrrolidinone

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후처리

1. 1
   기타68, preparation 61)
2. 2
   여과filtered through Arbocel®
3. 3
   기타The organic layer was separated
4. 4
   추출the aqueous extracted with ethyl acetate (2×250 mL)
5. 5
   세척washed with water and brine
6. 6
   건조dried over magnesium sulphate
7. 7
   농축The organics were concentrated in vacuo
8. 8
   기타the residue purified by column chromatography on silica gel eluting with toluene:ethyl acetate 100:0 to 98:2
9. 9
   기타The crude product was triturated with hexane:ether 66:33

실험 절차

2-Chloronicotinic acid methyl ester (WO 02/085358, pg. 21, example 1) (8.00 g, 47 mmol), caesium carbonate (21.30 g, 65 mmol) and copper iodide (890 mg, 4.7 mmol) were dissolved in a toluene:1-methyl-2-pyrrolidinone 4:1 mixture (155 mL) and the reaction mixture treated with 3-methylsulphanyl-phenol (6.21 g, 44 mmol) (WO 98/45268, pg. 68, preparation 61). The reaction mixture was heated td 110° C. for 18 hours. The reaction mixture was diluted with water (250 mL), and ethyl acetate (250 mL) and filtered through Arbocel®. The organic layer was separated and the aqueous extracted with ethyl acetate (2×250 mL). The organics were combined, washed with water and brine and dried over magnesium sulphate. The organics were concentrated in vacuo and the residue purified by column chromatography on silica gel eluting with toluene:ethyl acetate 100:0 to 98:2. The crude product was triturated with hexane:ether 66:33 to yield the title product, 4.90 g.

출처