4-Methylmorpholine → HCID 9949622, compound

HRID 1793756Notes

Reaction equation

HRID 1793756 reaction equation
[C:1]1(=[O:26])[N:5]([CH:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=2)[CH2:7][C:8]([NH2:10])=O)[C:4](=[O:21])[C:3]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:2]12.CN1CCOCC1.S(Cl)(Cl)=O>CN(C)C=O>[C:4]1(=[O:21])[N:5]([CH:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=2)[CH2:7][C:8]#[N:10])[C:1](=[O:26])[C:2]2=[CH:25][CH:24]=[CH:23][CH:22]=[C:3]12

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 24386Thionyl ChlorideHCID 461663CC-1069

Product 1

HCID 9949622HCID 9949622, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice bath cooled stirred suspension of 3-phthalimido-3-(3,4-dimethoxyphenyl)propionamide (1.77 g, 5.00 mmol) and 4-methylmorpholine (1.3 mL, 12 mmol) in dimethyformamide (17 mL) under nitrogen, was added thionyl chloride (0.7 mL, 9.6 mmol) dropwise via a syringe. There was a slight exotherm and after 30 minutes, the cooling bath was removed and the reaction mixture was stirred for 2 hours at room temperature. The reaction mixture was poured into a mixture of sodium bicarbonate (17 g) and 75 mL of ice water and stirred until the ice had melted. The slurry was filtered and the solid was washed with copious amounts of water. The wet solid was dissolved in methylene chloride (50 mL) and the organic layer was separated, dried over sodium sulfate, and concentrated in vacuo to afford an orange solid. The solid was purified by flash column chromatography (silica gel, 5/95 ethyl acetate/methylene chloride, 50 mm id column) to afford 1.32 g (79%) of the product as a white solid: 1H NMR (CDCl3) δ7.9–7.6 (m, 4H), 7.10 (m, 2H), 6.83 (m, 1H), 5.64 (dd, J=6.5, 10.2 Hz, 1H), 3.88 (s, 3H), 3.85 (s, 3H), 3.82 (dd, 1H), 3.30 (dd, J=6.5, 16.8 Hz, 1 H); 13C NMR (CDCl3) δ167.7, 149.5, 149.2, 134.4, 131.5, 129.1, 123.6, 120.1, 116.9, 111.1, 110.7, 56.0, 55.9, 51.1, 21.1. Anal. Calcd for C19H16N2O4 0.18 H2O. Theoretical: C, 76.2. H, 4.85; N, 8.25. Found: C, 67.23; H, 4.79; N, 8.27.

Workup

  1. temperatureTo an ice bath cooled
  2. customthe cooling bath was removed
  3. stirringthe reaction mixture was stirred for 2 hours at room temperature
  4. additionThe reaction mixture was poured into a mixture of sodium bicarbonate (17 g) and 75 mL of ice water
  5. stirringstirred until the ice
  6. filtrationThe slurry was filtered
  7. washthe solid was washed with copious amounts of water
  8. dissolutionThe wet solid was dissolved in methylene chloride (50 mL)
  9. customthe organic layer was separated
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated in vacuo
  12. customto afford an orange solid
  13. customThe solid was purified by flash column chromatography (silica gel, 5/95 ethyl acetate/methylene chloride, 50 mm id column)

Sources & evidence

ORD record
ord-09886d22a7e74f5ea13173d30ce9b9e8
Source dataset
uspto-grants-2006_07
Patent number
US07081464B2

Reaction notes

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