Water → 2-{[2-(Benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate

HRID 577476Notes

Reaction equation

HRID 577476 reaction equation
[H-].[Na+].[CH2:3]([N:5]([CH2:21][CH3:22])[C:6](=[O:20])[O:7][C:8]1[C:17]([Cl:18])=[C:16]2[C:11]([CH2:12][CH2:13][NH:14][C:15]2=[O:19])=[CH:10][CH:9]=1)[CH3:4].[CH2:23]([O:30][C:31]1[C:36]([CH2:37]Cl)=[C:35]([CH3:39])[CH:34]=[C:33]([CH3:40])[N:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.O>CN(C=O)C>[CH2:21]([N:5]([CH2:3][CH3:4])[C:6](=[O:20])[O:7][C:8]1[C:17]([Cl:18])=[C:16]2[C:11]([CH2:12][CH2:13][N:14]([CH2:37][C:36]3[C:31]([O:30][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[N:32][C:33]([CH3:40])=[CH:34][C:35]=3[CH3:39])[C:15]2=[O:19])=[CH:10][CH:9]=1)[CH3:22]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 612578682-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridineHCID 867237028-Chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate

Product 1

HCID 867237032-{[2-(Benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamateYield 99.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (2.2 g, 54 mmol, 60% in oil) in dry DMF (20 mL) was added dropwise a solution of 8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate (1f, 8.0 g, 27 mmol) in dry DMF (40 mL) at 0° C. under N2. The mixture was stirred at 0° C. for 15 minutes. 2-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 8.5 g, 32.4 mmol) was added. The mixture was stirred at room temperature overnight. To the reaction mixture was added dropwise H2O (200 mL) carefully. The mixture was extracted with EtOAc (2×150 mL). The combined organic layers were washed with brine (4×200 mL), dried over Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc, 3:1) to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate (1g, 14 g, 99%) as yellow oil.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. extractionThe mixture was extracted with EtOAc (2×150 mL)
  3. washThe combined organic layers were washed with brine (4×200 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by column chromatography (petroleum ether/EtOAc, 3:1)

Sources & evidence

ORD record
ord-6774825344fe4f919d7203fc8b22cda5
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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