Cesium carbonate → 2-(3-Phenylpropyl)-6-(3,3-diethoxypropyloxy)-1-oxo-1,2,3,4-tetrahydroisoquinoline

HRID 257052Notes

Reaction equation

HRID 257052 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][CH2:5]2.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:28]([O:30][CH:31]([O:35][CH2:36][CH3:37])[CH:32](Cl)[CH3:33])[CH3:29]>CN(C=O)C.O>[C:16]1([CH2:15][CH2:14][CH2:13][N:7]2[CH2:6][CH2:5][C:4]3[C:9](=[CH:10][CH:11]=[C:2]([O:1][CH2:33][CH2:32][CH:31]([O:35][CH2:36][CH3:37])[O:30][CH2:28][CH3:29])[CH:3]=3)[C:8]2=[O:12])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 189639836-Hydroxy-2-(3-phenylpropyl)-1-oxo-1,2,3,4-tetrahydroisoquinolineHCID 22601943Chloropropionaldehyde diethyl acetal

Product 1

HCID 189638682-(3-Phenylpropyl)-6-(3,3-diethoxypropyloxy)-1-oxo-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 6-hydroxy-2-(3-phenylpropyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline (7.55 g, 26.87 mmol), Cs2CO3 (18 g, 53.74 mmol) and chloropropionaldehyde diethyl acetal (5.4 mL, 32.2 mmol) in DMF (100 mL) is stirred for 48 hours. After this time the reaction is diluted with H2O (400 mL) and the resulting mixture extracted with EtOAc (2×200 mL). The combined organic phases are washed with saturated NaCl solution (2×400 mL), dried over MgSO4 and concentrated in vacuo. The residue is chromatographed (silica gel, 1:9 EtOAc/hexane) to give 2-(3-phenylpropyl)-6-(3,3-diethoxypropyloxy)-1-oxo-1,2,3,4-tetrahydroisoquinoline which is hydrolyzed with 6N HCl in tetrahydrofuran at room temperature to yield β-[2-(3-phenylpropyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yloxy]-propionaldehyde.

Workup

  1. extractionthe resulting mixture extracted with EtOAc (2×200 mL)
  2. washThe combined organic phases are washed with saturated NaCl solution (2×400 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is chromatographed (silica gel, 1:9 EtOAc/hexane)

Sources & evidence

ORD record
ord-2e9dd4b849754b3e9cfde1d5caf0e738
Source dataset
uspto-grants-1993_11
Patent number
US05260316

Reaction notes

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