Acetic Anhydride → N-(2-Methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)acetamide

HRID 1669184Notes

Reaction equation

HRID 1669184 reaction equation
[CH3:1][N:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([N+:12]([O-])=O)=[CH:7][CH:8]=2)[CH2:3]1.[CH3:15][C:16](OC(C)=O)=[O:17]>CCO.[Pd]>[CH3:1][N:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([NH:12][C:16](=[O:17])[CH3:15])=[CH:7][CH:8]=2)[CH2:3]1

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 221158282-Methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 25139890N-(2-Methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)acetamideYield 79.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

A solution of isoquinoline 252 (2.5 g, 13.0 mmol) in EtOH (200 mL) was stirred with Pd/C (5%, 200 mg) under H2 (35 psi) for 4 h. The solution was filtered through Celite, washed with EtOH (50 mL) and the solvent was evaporated. The residue was dissolved in dioxane (50 mL), Ac2O (2.7 mL, 28.6 mmol) was added and the solution stirred at 20° C. for 16 h. The solvent was evaporated and the residue was partitioned between dilute aqueous NH3 solution (50 mL) and DCM (50 mL). The aqueous layer was extracted with DCM (4×125 mL), the combined organic fraction dried and the solvent evaporated. The residue was purified by chromatography, eluting with 5% MeOH/DCM, to give acetamide 253 (2.1 g, 77%) as a brown solid: mp 157-159° C.; 1H NMR δ 7.29 (br s, 1H, H-8), 7.27 (br s, 1H, H-6), 7.22 (br s, 1H, NH), 7.12 (br d, J=8.1 Hz, 1H, H-5), 4.18 (d, J=16.2 Hz, 1H, H-1), 3.82 (d, J=16.1 Hz, 1H, H-1), 3.11-3.25 (m, 2H, H-3), 2.91-3.00 (m, 2H, H-4), 2.61 (s, 3H, NCH3), 2.16 (s, 3H, COCH3); 13C NMR δ 168.3, 136.6, 131.0, 129.2, 126.6, 119.2, 118.1, 61.5, 56.6, 47.3, 24.5, 24.0; MS (APCI) m/z 205 (MH+, 100%). Anal. calcd for C12H16N2O.½CH3OH.½H2O: C, 65.5; H, 8.4; N, 12.2. Found: C, 65.8; H, 8.8; N, 12.6%.

Workup

  1. filtrationThe solution was filtered through Celite
  2. washwashed with EtOH (50 mL)
  3. customthe solvent was evaporated
  4. dissolutionThe residue was dissolved in dioxane (50 mL)
  5. customThe solvent was evaporated
  6. customthe residue was partitioned between dilute aqueous NH3 solution (50 mL) and DCM (50 mL)
  7. extractionThe aqueous layer was extracted with DCM (4×125 mL)
  8. customthe combined organic fraction dried
  9. customthe solvent evaporated
  10. customThe residue was purified by chromatography
  11. washeluting with 5% MeOH/DCM

Sources & evidence

ORD record
ord-a168508653a14b839da51fb460015094
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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