Triethylamine → (+)-(1R,3R)-4-[3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester

HRID 1243202Notes

Reaction equation

HRID 1243202 reaction equation
[N:1]([C@@H:4]1[CH2:8][CH2:7][C@@H:6]([O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[CH2:5]1)=[N+]=[N-].[H][H].C(N(CC)CC)C.Cl[C:27]1[C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:31][N:30]=[C:29]([S:38][CH3:39])[N:28]=1>C(O)C.[Pt]=O>[CH2:36]([O:35][C:33]([C:32]1[C:31]([NH:1][C@@H:4]2[CH2:8][CH2:7][C@@H:6]([O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[CH2:5]2)=[N:30][C:29]([S:38][CH3:39])=[N:28][CH:27]=1)=[O:34])[CH3:37]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterHCID 21062582(-)-(1R,3R)-(3-azido-cyclopentyloxy)-tert-butyl-dimethyl-silaneHCID 178418361HCID 178418361, compound

Product 1

HCID 11750254(+)-(1R,3R)-4-[3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 82844Platinum oxide (PtO)CatalystHCID 702EthanolSolvent

Procedure

To a solution of (−)-(1R,3R)-(3-azido-cyclopentyloxy)-tert-butyl-dimethyl-silane (540 mg, 2.24 mmol) (from Example 27c supra) in ethanol (30 mL) was added platinum oxide (51 mg, 0.22 mmol) (Aldrich) and the mixture was hydrogenated under 1 atmosphere of hydrogen overnight. The mixture was then filtered, the solids were washed with tetrahydrofuran (approximately 25 mL) and the combined filtrate was concentrated to a residue that was dissolved in dioxane (50 mL). To that solution was added triethylamine (620 μL, 450 mg, 4.48 mmol) (Aldrich) and ethyl 4-chloro-2-methylthio-5-pyrimidinecarboxylate (520 mg, 2.24 mmol) (Aldrich) and the mixture was stirred at reflux for 1 hour. The reaction mixture was then cooled and partitioned between ethyl acetate and water. The ethyl acetate layer was collected, dried over sodium sulfate and concentrated to a residue that was purified by silica gel column chromatography with a 0–20% ethyl acetate in hexanes gradient to give (+)-(1R,3R)-4-[3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester as a colorless viscous oil. (Yield 710 mg, 77%).

Workup

  1. filtrationThe mixture was then filtered
  2. washthe solids were washed with tetrahydrofuran (approximately 25 mL)
  3. concentrationthe combined filtrate was concentrated to a residue that
  4. dissolutionwas dissolved in dioxane (50 mL)
  5. temperatureat reflux for 1 hour
  6. temperatureThe reaction mixture was then cooled
  7. custompartitioned between ethyl acetate and water
  8. customThe ethyl acetate layer was collected
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated to a residue that
  11. customwas purified by silica gel column chromatography with a 0–20% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-4b91daf4acaa4f0691bb0ec9ed923f44
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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