Morpholine → HCID 59441881, compound

HRID 1014357Notes

Reaction equation

HRID 1014357 reaction equation
[C:1]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][C:9]([N+:17]([O-:19])=[O:18])=[C:10]([O:15][CH3:16])[CH:11]=2)[CH2:6]1)(=[O:4])[CH:2]=[CH2:3].[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1>CO>[CH3:16][O:15][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][C:9]=1[N+:17]([O-:19])=[O:18])[CH2:6][N:5]([C:1](=[O:4])[CH2:2][CH2:3][N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)[CH2:14][CH2:13]2

Participants

4

Reactant 2

HCID 8083MorpholineHCID 594417802-Acryloyl-6-(methyloxy)-7-nitro-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 59441881HCID 59441881, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

A solution of 2-acryloyl-6-(methyloxy)-7-nitro-1,2,3,4-tetrahydroisoquinoline (425 mg, 1.62 mmol) in methanol (5 mL) was treated with morpholine (1.00 mL, 11.5 mmol, Aldrich) and heated at 65° C. in a sealed tube for 16 h. The mixture was cooled, concentrated, and partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic layer was separated, dried over magnesium sulfate, filtered, and purified by chromatography on SiO2 (dichloromethane to 25% methanol/dichloromethane) to give 6-(methyloxy)-2-[3-(4-morpholinyl)propanoyl]-7-nitro-1,2,3,4-tetrahydroisoquinoline. This material was taken directly to the next step without a determination of yield. 1H NMR (400 MHz, DMSO-d6) is complicated by amide rotomers δ ppm 2.32-2.41 (m, 4 H), 2.52-2.62 (m, 4 H), 2.79-2.97 (two app triplets at 2.83 and 2.94, 2 H), 3.48-3.58 (m, 4 H), 3.63-3.72 (m, 2 H), 3.89 (s, 3 H), 4.55-4.69 (two singlets at 4.57 and 4.67, 2 H), 7.18-7.21 (m, 1 H), 7.80 (s, 1 H); ESIMS (M+H)+=350.

Workup

  1. temperatureThe mixture was cooled
  2. concentrationconcentrated
  3. custompartitioned between ethyl acetate and saturated aqueous ammonium chloride
  4. customThe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. custompurified by chromatography on SiO2 (dichloromethane to 25% methanol/dichloromethane)

Sources & evidence

ORD record
ord-7374614c416049fa8a2ceed1cd7aa726
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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