Water → HCID 13759791, compound

HRID 1397311Notes

Reaction equation

HRID 1397311 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.[C-:11]#[N:12].[K+].[OH2:14]>Cl>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[C:5]1([C:11]#[N:12])[CH2:6][CH2:7][O:14][CH2:3][CH2:4]1

Participants

5

Reactant 3

HCID 962Water2×HCID 70461,2,3,4-TetrahydroisoquinolineHCID 9032Potassium Cyanide

Product 1

HCID 13759791HCID 13759791, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

3,4,5,6-Tetrahydro-4H-pyran-4-one (0.37 g, 3.75 mmol) was added to a solution of 1,2,3,4-tetrahydroisoquinoline (0.47 mL, 3.75 mmol) in conc. HCl (0.4 mL) diluted with ice water (1.5 mL), followed by a solution of KCN (0.24 g, 3.75 mmol) dissolved in water (2 mL), and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was then diluted with water and the organic product was extracted with EtOAc. The organic layer was washed with H2O and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica 60-120 mesh, eluent 6% EtOAc in petroleum ether) to afford 4-(3,4-dihydroisoquinolin-2(1H)-yl)tetrahydro-2H-pyran-4-carbonitrile (300 mg, yield 33%). 1H NMR (300 MHz, CDCl3) δ 7.19-7.11 (m, 3H), 7.07-7.05 (m, 1H), 4.10-4.04 (dt, J=12.3 Hz, 3.5 Hz, 2H), 3.87 (s, 2H), 3.76-3.68 (m, 2H), 2.97-2.91 (m, 4H), 2.28-2.23 (dd, J=13.3 Hz, 1.4 Hz, 2H), 1.93-1.84 (td, J=12.4 Hz, 4.2 Hz, 2H). MS (ESI) m/z: Calculated for C15H18N2O: 242.14. found: 243.2 (M+H)+.

Workup

  1. extractionthe organic product was extracted with EtOAc
  2. washThe organic layer was washed with H2O and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography (silica 60-120 mesh, eluent 6% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-b9fb2753eb074e03bf133103903ec979
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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