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

HRID 590451

反応式

HRID 590451 の反応式
CC(C)([O-])C.[Na+].[CH3:7][C@H:8]([OH:11])[CH2:9][CH3:10].F[C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)=[C:15]([NH2:28])[N:14]=1>C(OCC)(=O)C>[CH3:7][C@H:8]([O:11][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)=[C:15]([NH2:28])[N:14]=1)[CH2:9][CH3:10]

参加物

5

反応物 3

HCID 444683(+)-2-ButanolHCID 23676156Sodium t-butoxideHCID 592525662-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

生成物 1

HCID 592525572-{[(1S)-1-Methylpropyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine収率 78.8%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

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).

後処理

  1. customreaction
  2. temperatureAfter cooling the mixture
  3. washwashed with water (50 ml)
  4. extractionthe aqueous layer extracted again with ethyl acetate (50 ml)
  5. washThe combined organic extracts were washed with brine
  6. customdried
  7. customevaporated in vacuo (at 62° C.
  8. customto remove the excess alcohol)
  9. dissolutionThe residue (2.52 g) was dissolved in dichloromethane
  10. custompurified on an aminopropyl cartridge (110 g)
  11. washeluting with a 0-100% ethyl acetate in cyclohexane gradient over 60 mins
  12. customevaporated in vacuo

出典と根拠

ORDレコード
ord-a6040d15a2534c17b1b4313d8d4cf12d
出典データセット
uspto-grants-2016_01
特許番号
US09233962B2

関連ノート

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