反応 #67684

反応方程式

lithium bis(trimethylsilyl)amide

2-methyl-1-phenylpropan-2-yl-2-((4R,6S)-2,2-dimethyl-6-((1-phenyl-1H-tetrazol-5-ylsulfonyl)methyl)-1,3-dioxan-4-yl)acetate

N-(4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

ammonium chloride

→

title compound

収率 90.0%

2-methyl-1-phenylpropan-2-yl 2-((4R,6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate

収率 90.0%

溶媒

tetrahydrofuran

tetrahydrofuran

ethyl acetate

反応条件

後処理

1. 1
   workup.STIRRINGThen, the mixture was stirred for 4 hours
2. 2
   温度while warming to 0° C
3. 3
   workup.STIRRINGby stirring for 10 minutes
4. 4
   その他The organic layer was separated
5. 5
   洗浄washed successively with purified water (250 ml)
6. 6
   乾燥a saturated sodium bicarbonate aqueous solution (250 ml,) and a saturated sodium chloride aqueous solution (250 ml), dried over anhydrous magnesium sulfate
7. 7
   ろ過filtered
8. 8
   濃縮concentrated under reduced pressure
9. 9
   workup.STIRRINGThe resulting solid was stirred with isopropyl ether
10. 10
    ろ過filtered
11. 11
    その他collected
12. 12
    その他This solid was dried in a vacuum oven overnight (50° C., 200 mbar)

実験手順

2-methyl-1-phenylpropan-2-yl-2-((4R,6S)-2,2-dimethyl-6-((1-phenyl-1H-tetrazol-5-ylsulfonyl)methyl)-1,3-dioxan-4-yl)acetate (25.75 g) prepared in Example 15 and N-(4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide (15.55 g) were dissolved in tetrahydrofuran (60 ml), followed by cooling to −78° C. under an argon atmosphere, and lithium bis(trimethylsilyl)amide (120 ml of a 0.5M solution in tetrahydrofuran) was added thereto over 10 minutes, followed by stirring at the same temperature for 2 hours. Then, the mixture was stirred for 4 hours while warming to 0° C. A saturated ammonium chloride aqueous solution (250 ml) was added to the reaction liquid, followed by stirring for 10 minutes, and ethyl acetate (500 ml) was added thereto. The organic layer was separated and washed successively with purified water (250 ml), a saturated sodium bicarbonate aqueous solution (250 ml,) and a saturated sodium chloride aqueous solution (250 ml), dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting solid was stirred with isopropyl ether, filtered and collected. This solid was dried in a vacuum oven overnight (50° C., 200 mbar) to give the title compound (26.06 g, 90%).

出典