Acetamide → 1,2,3,4-Tetrahydroisoquinoline

HRID 2222227Notes

Reaction equation

HRID 2222227 reaction equation
[C:1]([NH2:4])(=O)[CH3:2].O=P(Cl)(Cl)Cl.[BH4-].[Na+].[C:12]1([CH3:18])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C(O)C>[CH2:18]1[C:12]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:2][CH2:1][NH:4]1

Participants

6

Reactant 4

HCID 178AcetamideHCID 1140TolueneHCID 24813Phosphorus oxychlorideHCID 4311764Sodium borohydride

Product 1

HCID 70461,2,3,4-TetrahydroisoquinolineYield 51%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Primary amine from example 1 (200 mg) was reacted with acetyl chloride (1.3 eq.) in dry ethylamine (3 eq.) and dry dichloromethane (5 ml) at 0° C. for 1 hour, then 25° C. for 14 hours and gave the acetamide in 88% yield. The acetamide (103 mg, 0.263 mmol) was refluxed for 3 hours with POCl3 (7.5 eq.) in dry toluene (10 ml) at 110° C. for 14 hours followed by NaBH4 reduction (11 eq.) in dry ethanol gave the corresponding 1,2,3,4-tetrahydroisoquinoline (50 mg, 51%). Demethylation as in example 1 gave the expected product as the hydrobromide salt (50 mg, 87%).

Sources & evidence

ORD record
ord-4fa18498237b446c87eeb0d570e042f7
Source dataset
uspto-grants-2008_05
Patent number
US07371762B2

Reaction notes

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