Methanol → Methyl 4-(allylamino)-5-amino-3-fluoro-2-(2-fluoro-4-iodophenylamino)benzoate

A stirred suspension of 4-allylamino-3-fluoro-2-(2-fluoro-4-iodo-phenylamino)-5-nitro-benzoic acid methyl ester (125.0 g, 0.25 mol), ammonium chloride (300.0 g, 8.58 mol) in 1:1 v/v mixture of methanol (4.0 lit) and dioxane (4.0 lit) was heated until it became a clear solution and was added iron powder (150.0 g, 2.68 mol) under a positive stream of nitrogen gas. The reaction mixture was refluxed for 16 h (completion of reaction is confirmed by TLC-EtOAc:Hexane/3:5) and poured onto a mixture of 10 kg of crushed ice and 6.5 L of saturated sodium bicarbonate. To the mixture was added 1 kg of Celite®, stirred and the thick suspension was filtered through a Celitetbed. The Celite® bed was rinsed with water, then with ethyl acetate and ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate (3 L) and the combined organic extracts are washed with water (3 L), brine (2 L), dried over anhydrous Na2SO4, filtered and evaporated under vacuum to give the title compound as oil (light brown color), which was used in the next step without further purification. Yield: 110 (93.55%)

1. temperaturewas heated until it
2. temperatureThe reaction mixture was refluxed for 16 h
3. additionTo the mixture was added 1 kg of Celite®
4. filtrationthe thick suspension was filtered through a Celitetbed
5. washThe Celite® bed was rinsed with water
6. customwith ethyl acetate and ethyl acetate layer was separated
7. extractionThe aqueous layer was extracted with ethyl acetate (3 L)
8. washthe combined organic extracts are washed with water (3 L), brine (2 L)
9. dry with materialdried over anhydrous Na2SO4
10. filtrationfiltered
11. customevaporated under vacuum

ORDレコード

ord-999181f8c8424048aa82a131e0450967

出典データセット

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07160915B2