反应详情

To a solution of 2-(2-(1-(2,6-dichlorophenyl)-1-methylethyl)-1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)-4-biphenylyl)-1H-imidazol-4-yl)-2-propanol (prepared in the manner described in PCT Publication No. WO 2010/138598, 1.98 g, 3.25 mmol) and di-tert-butyl diisopropylphosphoramidite (1.35 g, 4.87 mmol) in CH2CH2 (10 mL) was added tetrazole (0.569 g, 8.13 mmol). The resulting suspension was stirred at rt for about 16 hours. After this time, hydrogen peroxide (30%, 8.13 mmol) was added drop-wise and the resulting mixture was stirred for 2 hours. At the conclusion of this period, the reaction mixture was diluted with CH2CH2 (10 mL), washed with brine, dried and then concentrated to yield the crude product. The crude product was purified by column chromatography (hexane and acetone gradient; 9:1 to 1:1) to afford di-tert-butyl (4′-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-4-(2-hydroxypropan-2-yl)-1H-imidazol-1-yl)-3,3′-difluoro-5-(methylsulfonyl)biphenyl-4-yl)methyl phosphate (0.960 g, 1.20 mmol, 37% yield) as a white solid.

1. stirringthe resulting mixture was stirred for 2 hours
2. additionAt the conclusion of this period, the reaction mixture was diluted with CH2CH2 (10 mL)
3. washwashed with brine
4. customdried
5. concentrationconcentrated
6. customto yield the crude product
7. customThe crude product was purified by column chromatography (hexane and acetone gradient; 9:1 to 1:1)