Water → HCID 58128486, compound

HRID 1850709Notes

Reaction equation

HRID 1850709 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[CH:2].[Li][CH2:17][CH2:18][CH2:19][CH3:20].B(F)(F)F.[NH4+].[Cl-].[OH2:27]>C1COCC1>[CH2:17]([O:27][CH2:13][C@H:12]([OH:11])[CH2:14][C:2]#[C:1][CH:3]1[CH2:4][CH2:5][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:7][CH2:8]1)[C:18]1[CH:3]=[CH:1][CH:2]=[CH:20][CH:19]=1

Participants

7

Reactant 5

HCID 962WaterHCID 6356Boron trifluorideHCID 25517Ammonium ChlorideHCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 58128486HCID 58128486, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Commercially available tert-butyl 4-ethynylpiperidine-1-carboxylate was dissolved in 40 ml of THF and cooled to −78° C. forming a white slurry. Titrated n-BuLi (2.2 M in hexanes, 23.9 ml, 52.6 mmol) was added dropwise with stirring. The clear colorless solution was stirred at −78° C. for 5 minutes. A solution of the R-(+) benzyl glycidyl epoxide (8.63 g, 52.6 mmol) in THF (20 ml) was added dropwise. BF3 etherate (8.43 g, 59.7 mmol) was then added dropwise with a syringe and the solution stirred at −78° C. for 1 hour. Sat'd aq. NH4Cl was added (100 ml), the mixture warmed to RT, diluted with water to dissolve any remaining solids, and extracted with iPrOAc (3×100 ml). The organic fractions were combined, washed with brine, dried over MgSO4, filtered and stripped. Crude product was purified by chromatography on SiO2 eluting with 30% EtOAc:Hexanes. The alcohol was repurified by chromatography on a C18 reversed phase column (12-100% water:acetonitrile 0.1% TFA as two runs.). Product containing fractions were combined, reduced in volume by approximately 50%, —made basic by addition of sat'd aq. NaHCO3, water was added to dissolve some white solids, and the mixture extracted with iPrOAc (3×100). The organic fractions were combined, washed with brine, dried over MgSO4, filtered, and stripped.

Workup

  1. customforming a white slurry
  2. stirringThe clear colorless solution was stirred at −78° C. for 5 minutes
  3. stirringthe solution stirred at −78° C. for 1 hour
  4. temperaturethe mixture warmed to RT
  5. dissolutionto dissolve any remaining solids
  6. extractionextracted with iPrOAc (3×100 ml)
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customCrude product was purified by chromatography on SiO2 eluting with 30% EtOAc
  11. customThe alcohol was repurified by chromatography on a C18 reversed phase column (12-100% water:acetonitrile 0.1% TFA as two runs.)
  12. additionProduct containing fractions
  13. additionreduced in volume by approximately 50%, —made basic by addition of sat'd aq. NaHCO3, water
  14. additionwas added
  15. dissolutionto dissolve some white solids
  16. extractionthe mixture extracted with iPrOAc (3×100)
  17. washwashed with brine
  18. dry with materialdried over MgSO4
  19. filtrationfiltered

Sources & evidence

ORD record
ord-428b180237d540d3a46eeeb05214ce0e
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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