반응 #60265

반응 방정식

cyclopropyl methyl hydroxylamine hydrochloride

PyBOP

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid

Hunig's base

→

pure desired product

수율 70.0%

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

수율 70.0%

용매

ethyl acetate

THF methylene chloride

반응 조건

후처리

1. 1
   workup.ADDITIONis added
2. 2
   workup.WAITAfter 16 hours
3. 3
   세척washed with 0.1 N HCl, saturated NaHCO3, and brine
4. 4
   건조The organic layer is dried (Na2SO4)
5. 5
   농축concentrated under reduced pressure
6. 6
   기타The crude yellow residue is purified by FCC
7. 7
   세척eluted with ethyl acetate

실험 절차

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid 10d (0.390 g, 0.902 mmol) is dissolved in 1:1 THF/methylene chloride (6 mL) and Hunig's base (0.346 mL, 1.985 mmol) is added followed by PyBOP (0.563 g, 1.083 mmol). After 10 minutes, cyclopropyl methyl hydroxylamine hydrochloride (0.134 g, 1.083 mmol) is added. After 16 hours, the reaction mixture is diluted with ethyl acetate and washed with 0.1 N HCl, saturated NaHCO3, and brine. The organic layer is dried (Na2SO4) and concentrated under reduced pressure. The crude yellow residue is purified by FCC eluted with ethyl acetate to give 0.315 g (70%) pure desired product as a yellow solid: MS APCI (+) m/z 503, 501 (M+1 Br pattern) detected.

출처