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

HRID 1243210Notes

Reaction equation

HRID 1243210 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 21062583(+)-(1S,3S)-(3-azido-cyclopentyloxy)-tert-butyl-dimethyl-silaneHCID 178418361HCID 178418361, compound

Product 1

HCID 11338879(-)-(1S,3S)-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 (+)-(1S,3S)-(3-azido-cyclopentyloxy)-tert-butyl-dimethyl-silane (580 mg, 2.40 mmol) (from Example 29c supra) in ethanol (30 mL) was added platinum oxide (55 mg, 0.24 mmol) (Aldrich). The mixture was hydrogenated under 1 atmosphere of hydrogen overnight. The reaction mixture was then filtered, the solids were washed with tetrahydrofuran (approximately 30 mL) and the combined filtrate was concentrated to a residue that was dissolved in dioxane (50 mL). To this solution was added triethylamine (970 μL, 705 mg, 6.96 mmol) (Aldrich) and ethyl 4-chloro-2-methylthio-5-pyrimidinecarboxylate (594 mg, 2.55 mmol) (Aldrich) and the mixture was heated at reflux for 45 minutes then cooled and partitioned between ethyl acetate and water. The organic layer was collected, dried over sodium sulfate, filtered and concentrated to a residue that was purified by chromatography on a silica gel column with a 0–20% ethyl acetate in hexanes gradient to give (−)-(1S,3S)-4-[3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester as a colorless viscous oil. (Yield 910 mg, 95%).

Workup

  1. filtrationThe reaction mixture was then filtered
  2. washthe solids were washed with tetrahydrofuran (approximately 30 mL)
  3. concentrationthe combined filtrate was concentrated to a residue that
  4. dissolutionwas dissolved in dioxane (50 mL)
  5. temperaturethe mixture was heated
  6. temperatureat reflux for 45 minutes
  7. temperaturethen cooled
  8. custompartitioned between ethyl acetate and water
  9. customThe organic layer was collected
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to a residue that
  13. customwas purified by chromatography on a silica gel column with a 0–20% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-eda46598c3e84181a0b0ff5b65c693ce
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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