(2S)-hexan-2-ol → 2-{[(1S)-1-Methylpentyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 1616287Notes

Reaction equation

HRID 1616287 reaction equation
CC(C)([O-])C.[Na+].[CH3:7][C@H:8]([OH:13])[CH2:9][CH2:10][CH2:11][CH3:12].F[C:15]1[N:23]=[C:22]2[C:18]([N:19]=[CH:20][N:21]2[CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)=[C:17]([NH2:30])[N:16]=1>COCCOC>[CH3:7][C@H:8]([O:13][C:15]1[N:23]=[C:22]2[C:18]([N:19]=[CH:20][N:21]2[CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)=[C:17]([NH2:30])[N:16]=1)[CH2:9][CH2:10][CH2:11][CH3:12]

Participants

5

Reactant 3

HCID 638097(2S)-hexan-2-olHCID 23676156Sodium t-butoxideHCID 592525662-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 592526582-{[(1S)-1-Methylpentyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amineYield 41.2%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

Sodium t-butoxide (4.86 g, 50.6 mmol) was added portionwise to a stirred mixture of (S)-2-hexanol (12 g, 117 mmol) and 1,2-dimethoxyethane (12 ml). The resultant mixture was heated to 50° C. under an atmosphere of nitrogen and then 2-fluoro -9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (3 g, 12.65 mmol) was added. The resultant mixture was maintained at 50° C. for 20 hours when LCMS indicated complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with water (100 ml) then saturated brine (50 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.665 g).

Workup

  1. customreaction
  2. custompartitioned between ethyl acetate (100 ml) and water (100 ml)
  3. washThe organic phase was washed with water (100 ml)
  4. dry with materialsaturated brine (50 ml), dried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residue was dissolved in dichloromethane
  8. custompurified on an aminopropyl (NH2) cartridge (100 g)
  9. washeluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-b03e938bb0124858bbdec8be06bc2205
Source dataset
uspto-grants-2014_07
Patent number
US08765772B2

Reaction notes

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