Ethyl Acetate → 2-Butoxy-8-methoxy-9-(tetrahydrofuran-3-ylmethyl)-9H-purin-6-amine

HRID 1010933Notes

Reaction equation

HRID 1010933 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[NH:19]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11].CS(O[CH2:30][CH:31]1[CH2:35][CH2:34][O:33][CH2:32]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CS(C)=O.O.[Cl-].[Na+].O>[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:30][CH:31]2[CH2:35][CH2:34][O:33][CH2:32]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 22273010(Tetrahydrofuran-3-yl)methyl methanesulfonateHCID 178450370HCID 178450370, compound

Product 1

HCID 576996032-Butoxy-8-methoxy-9-(tetrahydrofuran-3-ylmethyl)-9H-purin-6-amineYield 101.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 2-butoxy-8-methoxy-9H-purin-6-amine trifluoroacetate salt (4.5 g), tetrahydro-3-furanylmethyl methanesulfonate (2.77 g) and potassium carbonate (5.31 g) in dimethyl sulfoxide (45 ml) was stirred and heated at 60° C. for 1.5 hours, followed by heating at 90° C. for 2.5 hours. The reaction was allowed to cool and the mixture diluted with water and brine, and shaken with ethyl acetate. The insoluble solid present was filtered (209 mg of product) and the organic layer separated. The aqueous layer was further extracted four times with ethyl acetate. The combined organic layers were washed with water and then brine. The organic layer was dried by passing through a hydrophobic frit and concentrated in vacuo to yield a light brown solid (4.18 g). This was recrystallised from acetonitrile (25 ml) to afford the product (2.28 g). This was further purified by dissolving in dichloromethane and washing with 1M hydrochloric acid, brine and saturated sodium hydrogencarbonate. The organic layer was dried through a hydrophobic frit and concentrated in vacuo to yield the product as a cream coloured solid (2.03 g).

Workup

  1. temperatureby heating at 90° C. for 2.5 hours
  2. temperatureto cool
  3. filtrationThe insoluble solid present was filtered (209 mg of product)
  4. customthe organic layer separated
  5. extractionThe aqueous layer was further extracted four times with ethyl acetate
  6. washThe combined organic layers were washed with water
  7. customThe organic layer was dried
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-45682bb96d5340fdb55fa7c8f0cf37fb
Source dataset
uspto-grants-2011_07
Patent number
US07977344B2

Reaction notes

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