反応 #40399

反応方程式

sodium hydrogen carbonate

6-benzyloxy-8-(2,2-dihydroxyacetyl)-4H-benzo[1,4]oxazin-3-one

2-(4-fluorophenyl)-1,1-dimethylethylamine

sodium borohydride

→

ethanolamine

8-{2-[2-(4-fluorophenyl)-1,1-dimethylethylamino]-1-hydroxyethyl}-6-hydroxy-4H-benzo[1,4]oxazin-3-one

溶媒

ethanol

反応条件

後処理

1. 1
   workup.ADDITIONMolecular sieve was added
2. 2
   温度After cooling to ambient temperature
3. 3
   抽出was extracted with ethyl acetate
4. 4
   その他The organic phases were evaporated down
5. 5
   その他the residue was chromatographed (eluent: hexane-ethyl acetate-methanol)

実験手順

300 mg (0.91 mmol) of 6-benzyloxy-8-(2,2-dihydroxyacetyl)-4H-benzo[1,4]oxazin-3-one and 183 mg (1.09 mmol) of 2-(4-fluorophenyl)-1,1-dimethylethylamine were dissolved in 3 mL of ethanol. Molecular sieve was added and the mixture was heated to 80° C. for 30 minutes. After cooling to ambient temperature, 35 mg (0.91 mmol) of sodium borohydride was added. The mixture was stirred for 1 hour at ambient temperature, then sodium hydrogen carbonate solution was added to the reaction mixture and it was extracted with ethyl acetate. The organic phases were evaporated down and the residue was chromatographed (eluent: hexane-ethyl acetate-methanol). The ethanolamine thus obtained (223 mg) was dissolved in methanol to cleave the benzyl protecting group and hydrogenated with 150 mg palladium hydroxide as catalyst at ambient temperature and normal pressure. The catalyst was separated off by filtering through CELITE® filter agent, the filtrate was freed from solvent and the residue was chromatographed (silica gel; eluent: dichloromethane-methanol). Beige solid. Yield: 76 mg (22%); mass spectrometry: [M+H]+=375.

出典