Triethylamine → tert-Butyl 4-phenyl-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1942508Notes

Reaction equation

HRID 1942508 reaction equation
Cl.[C:2]1([C:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH:13]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:21](=O)([O:27]C(C)(C)C)[O:22][C:23]([CH3:26])([CH3:25])[CH3:24]>C(#N)C>[C:2]1([C:8]2[CH2:13][CH2:12][N:11]([C:21]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:27])[CH2:10][CH:9]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27238604-Phenyl-1,2,3,6-tetrahydropyridine hydrochlorideHCID 10219638Carbonic acid, bis(1,1-dimethylethyl) ester

Product 1

HCID 15442738tert-Butyl 4-phenyl-3,6-dihydropyridine-1(2H)-carboxylateYield 97.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (354.6 g) in acetonitrile (12 L) was added triethylamine (366.9 g) at 20° C. in a water-bath, and the mixture was stirred for 15 minutes. To the reaction solution was added dropwise a solution of di-t-butyl carbonate (474.5 g) in acetonitrile (700 ml) at 15˜19° C. in a water-bath, and further thereto was added N,N-dimethylamino-pyridine (11.06 g). The mixture was stirred at room temperature for 12 hours, and the solvent was removed by evaporation under reduced pressure. The obtained residue was diluted with methylene chloride (10 L), and washed with 1M hydrochloric acid (×3) and 5% saturated aqueous sodium hydrogen carbonate solution, dried over anhydrous sodium hydrogen sulfate, and the solvent was evaporated under reduced pressure to give a crude product (470.6 g). The obtained crude product was purified by silica gel column chromatography (methylene chloride/methanol=1/0→50/1) to give the title compound (456.8 g).

Workup

  1. stirringThe mixture was stirred at room temperature for 12 hours
  2. customthe solvent was removed by evaporation under reduced pressure
  3. additionThe obtained residue was diluted with methylene chloride (10 L)
  4. washwashed with 1M hydrochloric acid (×3) and 5% saturated aqueous sodium hydrogen carbonate solution
  5. dry with materialdried over anhydrous sodium hydrogen sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customto give a crude product (470.6 g)
  8. customThe obtained crude product
  9. customwas purified by silica gel column chromatography (methylene chloride/methanol=1/0→50/1)

Sources & evidence

ORD record
ord-e117238fcfb041d1bb385b6ba4512733
Source dataset
uspto-grants-2013_03
Patent number
US08389511B2

Reaction notes

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