Acetic Acid → HCID 58042413, compound

HRID 2048041Notes

Reaction equation

HRID 2048041 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.C([Li])CCC.CCCCCC.B(OC)(OC)[O:26]C.C(O)(=O)C.OO.S(=O)(O)[O-].[Na+]>C1COCC1>[N:8]1([C:5]2[N:4]=[CH:3][C:2]([OH:26])=[CH:7][N:6]=2)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1

Participants

9

Reactant 7

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 8058HexaneHCID 8470Trimethyl borateHCID 36146825-Bromo-2-(piperidin-1-yl)pyrimidineHCID 23665763Sodium BisulfiteHCID 178418339Butyllithium

Product 1

HCID 58042413HCID 58042413, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 5-bromo-2-piperidin-1-ylpyrimidine (1.00 g, 4.15 mmol) in freshly distilled THF (5.2 mL), was purged with argon and cooled to −78° C. To the cooled reaction mixture was added drop-wise a solution of n-butyllithium in hexane (2.5 M, 1.99 mL, 4.98 mmol). The reaction mixture was stirred at −78° C. for 10 minutes and then added dropwise over 10 minutes to a solution of trimethyl borate (0.559 mL, 4.98 mmol) in THF (5.2 mL), which had been purged with argon and cooled to 0° C. The resulting reaction mixture was stirred at 0° C. for a further 20 minutes, followed by addition of acetic acid (0.356 mL, 6.22 mmol). After a further 5 minutes of stirring, a 30% aqueous solution of hydrogen peroxide (0.517 mL, 4.57 mmol) was added dropwise and stirring continued at 0° C. for 5 minutes. A saturated aqueous solution of sodium bisulfite (50 mL) was added and the mixture extracted with EtOAc. The organic extract was washed with a saturated aqueous brine solution, dried over anhydrous sodium sulfate, filtered over Celite™ and concentrated in vacuo. The crude material was purified using silica gel chromatography eluting with 25% EtOAC in hexane to afford the title compound (728 mg, 98%):

Workup

  1. customTo the cooled reaction mixture
  2. customhad been purged with argon
  3. temperaturecooled to 0° C
  4. customThe resulting reaction mixture
  5. stirringwas stirred at 0° C. for a further 20 minutes
  6. stirringAfter a further 5 minutes of stirring
  7. stirringstirring
  8. waitcontinued at 0° C. for 5 minutes
  9. extractionthe mixture extracted with EtOAc
  10. extractionThe organic extract
  11. washwas washed with a saturated aqueous brine solution
  12. dry with materialdried over anhydrous sodium sulfate
  13. filtrationfiltered over Celite™
  14. concentrationconcentrated in vacuo
  15. customThe crude material was purified
  16. washeluting with 25% EtOAC in hexane

Sources & evidence

ORD record
ord-90d174a053874999a5326e325c7d0af3
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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