Triethylamine → Tert-butyl 4-[1-hydroxy-3-(6-methylpyridin-2-yl)prop-2-ynyl]piperidine-1-carboxylate

HRID 1895963Notes

Reaction equation

HRID 1895963 reaction equation
C(N(CC)CC)C.[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[N:11]=1)#[CH:9].[C:17]([N:24]1[CH2:29][CH2:28][CH:27]([CH:30]=[O:31])[CH2:26][CH2:25]1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>C1(C)C=CC=CC=1.O.FC(F)(F)S([O-])(=O)=O.[Zn+2].FC(F)(F)S([O-])(=O)=O>[OH:31][CH:30]([CH:27]1[CH2:28][CH2:29][N:24]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:25][CH2:26]1)[C:9]#[C:8][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[N:11]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 134006352-Ethynyl-6-methylpyridine

Product 1

HCID 68725592Tert-butyl 4-[1-hydroxy-3-(6-methylpyridin-2-yl)prop-2-ynyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 104671Zinc trifluoromethanesulfonateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

A mixture of zinc trifluoromethanesulfonate (0.07 g, 0.19 mmol) and triethylamine (0.065 mL, 0.47 mmol) in anhydrous toluene (5 mL) was stirred at room temperature under nitrogen atmosphere. After 1 h, 2-ethynyl-6-methyl-pyridine (0.13 g, 1.13 mmol) prepared as described in WO200544267 was added and after 15 min was dropped a solution of 1-Boc-4-piperidinecarboxaldehyde (0.2 g, 0.938 mmol) in toluene (1 mL): the resulting mixture was heated at 100° C. for 6 h. Afterwards, it was cooled to r.t., diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried on Na2SO4 and evaporated to dryness in vacuo to give a crude, which was purified twice by automated flash liquid chromatography (Horizon™-Biotage) eluting with CHCl3-MeOH 98-2 affording the title product (0.13 g) as a brown oil.

Workup

  1. additionwas added and after 15 min
  2. temperaturethe resulting mixture was heated at 100° C. for 6 h
  3. temperatureAfterwards, it was cooled to r.t.
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. customdried on Na2SO4
  7. customevaporated to dryness in vacuo
  8. customto give a crude, which
  9. customwas purified twice by automated flash liquid chromatography (Horizon™-Biotage)
  10. washeluting with CHCl3-MeOH 98-2 affording the title product (0.13 g) as a brown oil

Sources & evidence

ORD record
ord-5bd6e83cd0a845898cfbacfe8ac0207b
Source dataset
uspto-grants-2013_08
Patent number
US08518916B2

Reaction notes

Loading…