Cyclohexanemethanol → HCID 57699724, compound

HRID 1011017Notes

Reaction equation

HRID 1011017 reaction equation
[CH:1]1([CH2:7][OH:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C)([O-])C.[Na+].Cl[C:16]1[N:24]=[C:23]2[C:19]([N:20]=[CH:21][N:22]2[CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)=[C:18]([NH2:31])[N:17]=1>COCCOC.O>[CH:1]1([CH2:7][O:8][C:16]2[N:24]=[C:23]3[C:19]([N:20]=[CH:21][N:22]3[CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][O:26]3)=[C:18]([NH2:31])[N:17]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 7507CyclohexanemethanolHCID 127778192-Chloro-9-(tetrahydropyran-2-yl)adenineHCID 23676156Sodium t-butoxide2×

Product 1

HCID 57699724HCID 57699724, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
93 °C

Procedure

Cyclohexylmethanol (4.5784 g) was diluted with 1,2-dimethoxyethane (99%+) (20 mL) before sodium tert-butoxide (3.853 g) was added gradually with stirring under nitrogen. An exotherm was observed on addition of sodium tert-butoxide. 2-Chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2.5428 g) was added and the resultant mixture was heated to reflux at 93° C. (internal). A further quantity of 1,2-dimethoxyethane (99%+) (20 mL) was added to help dissolution and refluxed overnight. The reaction mixture was dissolved in water (100 mL) and extracted with ethyl acetate (100 mL, twice). The combined organic extracts were washed with brine (100 mL) before the organic layer was separated and dried by passing through a hydrophobic frit. Evaporated volatiles under reduced pressure and then azeotroped with toluene (50 mL, twice) to give mobile amber oil. This material was purified by silica chromatography (ISCO) eluting with 0-100% ethyl acetate: cyclohexane). This gave the title compound after placing under vacuo as pale yellow foam (1.0364 g) (94% purity by LCMS, 6% 2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine) and was used in next step without further purification.

Workup

  1. additionwas added gradually
  2. dissolutiondissolution
  3. temperaturerefluxed overnight
  4. extractionextracted with ethyl acetate (100 mL
  5. washThe combined organic extracts were washed with brine (100 mL) before the organic layer
  6. customwas separated
  7. customdried
  8. customEvaporated volatiles under reduced pressure and then azeotroped with toluene (50 mL
  9. customtwice) to give mobile amber oil
  10. customThis material was purified by silica chromatography (ISCO)
  11. washeluting with 0-100% ethyl acetate

Sources & evidence

ORD record
ord-a10ec333d0ea453184b34a31456b9ea5
Source dataset
uspto-grants-2011_07
Patent number
US07977344B2

Reaction notes

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