反応 #649929

反応方程式

Sodium t-butoxide

2-propanol

2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

→

solid

収率 98.4%

2-[(1-Methylethyl)oxy]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

収率 98.4%

溶媒

ethyl acetate

反応条件

後処理

1. 1
   温度the reaction mixture heated
2. 2
   workup.STIRRINGstirred at 50° C. for 4 hours
3. 3
   洗浄washed with water (3×25 ml)
4. 4
   抽出the combined aqueous layers extracted again with ethyl acetate (2×25 ml)
5. 5
   その他The combined organic layers were dried by passage through a hydrophobic frit
6. 6
   ろ過filtered
7. 7
   その他evaporated

実験手順

Sodium t-butoxide (1.30 g, 13.53 mmol) was added to 2-propanol (16.95 ml, 220 mmol) portionwise with stirring over 5 mins. 2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2 g, 8.43 mmol) was added and the reaction mixture heated and stirred at 50° C. for 4 hours and then allowed to cool to room temperature. The reaction mixture was then diluted with ethyl acetate (75 ml), washed with water (3×25 ml) and the combined aqueous layers extracted again with ethyl acetate (2×25 ml). The combined organic layers were dried by passage through a hydrophobic frit, filtered and evaporated to give an off-white solid (2.30 g). This material was dissolved in dichloromethane and purified using an aminopropyl SPE cartridge (70 g) eluted with a 0-100% ethyl acetate in cyclohexane gradient. The appropriate fractions were combined and evaporated to give a white solid (1.6 g) which was further purified by column chromatography using a reverse phase (C18) Flashmaster II system loading in 1:1 MeOH/DMSO and eluting with 0-50% acetonitrile (+0.1% TFA) in water (+0.1% TFA) gradient over 40 mins. collecting fractions in vials containing ca. 2 mL of saturated aqueous sodium bicarbonate solution. The appropriate fractions were combined, and extracted with dichloromethane (3×100 mL). The combined organic extracts were dried by passage through a hydrophobic frit and evaporated to give the title compound as a white solid (888 mg).

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