تفاعل #67684

معادلة التفاعل

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

المردود 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

المردود 90.0%

المذيبات

tetrahydrofuran

tetrahydrofuran

ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGThen, the mixture was stirred for 4 hours
2. 2
   درجة الحرارةwhile warming to 0° C
3. 3
   workup.STIRRINGby stirring for 10 minutes
4. 4
   أخرىThe organic layer was separated
5. 5
   غسيلwashed successively with purified water (250 ml)
6. 6
   تجفيفa saturated sodium bicarbonate aqueous solution (250 ml,) and a saturated sodium chloride aqueous solution (250 ml), dried over anhydrous magnesium sulfate
7. 7
   ترشيحfiltered
8. 8
   تركيزconcentrated under reduced pressure
9. 9
   workup.STIRRINGThe resulting solid was stirred with isopropyl ether
10. 10
    ترشيحfiltered
11. 11
    أخرىcollected
12. 12
    أخرىThis solid was dried in a vacuum oven overnight (50° C., 200 mbar)

الإجراء التجريبي

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%).

المصدر