Sulfuric Acid → N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide

HRID 45669Notes

Reaction equation

HRID 45669 reaction equation
[Cl:1][C:2]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:3]=1[CH2:4][N:5]([CH3:19])[CH2:6][CH:7]([C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:18])[CH3:17])=[CH:11][CH:10]=1)O.S(=O)(=O)(O)O>ClCCl>[Cl:24][C:22]1[CH:21]=[C:20]2[C:3](=[C:2]([Cl:1])[CH:23]=1)[CH2:4][N:5]([CH3:19])[CH2:6][CH:7]2[C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:18])[CH3:17])=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 12149184N-(4-(2-((2,4-dichlorobenzyl)(methyl)amino)-1-hydroxyethyl)phenyl)acetamide

Product 1

HCID 9902940N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Into a 100-mL 3-necked round-bottom flask, was placed a solution of N-(4-(2-((2,4-dichlorobenzyl)(methyl)amino)-1-hydroxyethyl)phenyl)acetamide (500 mg, 1.36 mmol, 1.00 equiv) in dichloromethane (3 mL). This was followed by the addition of sulfuric acid (3 mL) dropwise with stirring at 0° C. The resulting solution was stirred for 5 h at 0-5° C. The reaction was then quenched by the addition of 20 mL of water/ice. The pH value of the solution was adjusted to 7-8 with sodium hydroxide. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10-1:5). This resulted in 25 mg (5%) of N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide as a white solid. 1H-NMR (300 HMz, CDCl3, ppm): δ 7.46-7.49 (2H, d, J=8.4 Hz), 7.23-7.29 (1H, m), 7.12-7.15 (2H, d, J=8.4 Hz), 6.80 (1H, s), 4.314 (1H, s), 3.92 (1H, d), 3.58-3.63 (1H, d), 3.06 (1H, s), 2.61-2.68 (1H, m), 2.57 (3H, s), 2.20 (3H, s). MS (ES, m/z): 349 [M+H]+.

Workup

  1. customInto a 100-mL 3-necked round-bottom flask, was placed
  2. stirringThe resulting solution was stirred for 5 h at 0-5° C
  3. customThe reaction was then quenched by the addition of 20 mL of water/ice
  4. extractionThe resulting solution was extracted with 3×20 mL of ethyl acetate
  5. concentrationconcentrated under vacuum
  6. customThis resulted in 25 mg (5%) of N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide as a white solid

Sources & evidence

ORD record
ord-85bce67ce258474e8baeb04f1963a199
Source dataset
uspto-grants-2013_09
Patent number
US08541448B2

Reaction notes

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