反応 #649919

反応方程式

Sodium tert-butoxide

(2S)-2-butanol

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

→

title compound

収率 78.8%

2-{[(1S)-1-Methylpropyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

収率 78.8%

溶媒

ethyl acetate

反応条件

後処理

1. 1
   その他reaction
2. 2
   温度After cooling the mixture
3. 3
   洗浄washed with water (50 ml)
4. 4
   抽出the aqueous layer extracted again with ethyl acetate (50 ml)
5. 5
   洗浄The combined organic extracts were washed with brine
6. 6
   その他dried
7. 7
   その他evaporated in vacuo (at 62° C.
8. 8
   その他to remove the excess alcohol)
9. 9
   workup.DISSOLUTIONThe residue (2.52 g) was dissolved in dichloromethane
10. 10
    その他purified on an aminopropyl cartridge (110 g)
11. 11
    洗浄eluting with a 0-100% ethyl acetate in cyclohexane gradient over 60 mins
12. 12
    その他evaporated in vacuo

実験手順

Sodium tert-butoxide (3.24 g, 33.7 mmol) was added portionwise with stirring to (2S)-2-butanol (10 g, 135 mmol). 2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2 g, 8.43 mmol) was added to the resulting suspension and the mixture heated to 50° C. for 6 hours when LCMS showed complete reaction. After cooling the mixture was diluted with ethyl acetate (100 ml), and washed with water (50 ml) and the aqueous layer extracted again with ethyl acetate (50 ml). The combined organic extracts were washed with brine, dried using a hydrophobic frit and evaporated in vacuo (at 62° C. to remove the excess alcohol). The residue (2.52 g) was dissolved in dichloromethane and purified on an aminopropyl cartridge (110 g) using a Flashmaster II apparatus and eluting with a 0-100% ethyl acetate in cyclohexane gradient over 60 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white solid (1.935 g).

出典