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

HRID 527797

Reaction equation

HRID 527797 reaction equation
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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-a7b57e4716424a25b5da503e829631f7
Source dataset
uspto-grants-2016_05
Patent number
US09346806B2

Linked notes

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