Methylamine → Ammonia

HRID 266637Notes

Reaction equation

HRID 266637 reaction equation
[CH:1]([C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][C@@H:6]([N:13]([CH:17]([CH3:19])[CH3:18])[CH2:14][CH2:15][CH3:16])[CH2:7][O:8]2)=O.S([CH2:30][N+:31]#[C-:32])(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[CH3:39][NH2:40]>CO>[NH3:13].[CH3:30][N:31]1[C:1]([C:3]2[CH:12]=[CH:11][CH:10]=[C:9]3[C:4]=2[CH2:5][C@@H:6]([N:13]([CH:17]([CH3:19])[CH3:18])[CH2:14][CH2:15][CH3:16])[CH2:7][O:8]3)=[CH:39][N:40]=[CH:32]1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 11430Potassium Carbonate2×HCID 161915Tosylmethyl isocyanide3×HCID 53900286HCID 53900286, compound

Product 2

HCID 222AmmoniaYield 0.5%HCID 53706274HCID 53706274, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(R)-5-Formyl-3-(N-isopropyl-N-n-propylamino)chroman (0.4 g, 1.5 mmol) was dissolved in methanol (15 mL), saturated with methylamine. Some molcular sieves (3 Å) were added. The solvent was removed in vacuo. The residue was dissolved in methanol (30 mL) under nitrogen atmosphere. Tosylmethylisocyanide (0.36 g, 1.8 mmol) and K2CO3 (0.25 g, 1.8 mmol) were added and the reaction mixture was reluxed for 1 hour. Additionally tosylmethylisocyanide (0.36 g, 1.8 mmol) and K2CO3 (0.25 g, 1.8 mmol) were added and the reflux was continued for 3 hours. Tosylmethylisocyanide (0.1 g, 5.2 mmol) was added once more and the reflux was continued for 12 hours. The solvent was removed in vacuo. The residue was dissolved in diethyl ether/2M NH3. The layers were separated and the water-phase was extracted once more with ether. The organic layers were combined and dried (Na2SO4). The solvent was removed in vacuo to give a brown oily residue which was purified by flash chromatography (SiO2, first CH2Cl2 /EtOAc, 5:1, also containing 0.5% of NH3 and then EtOAc/EtOH, 50:1+0.5% of NH3) to give 200 mg of the title compound (42 yield). [α]D21 -37° (c 30 mg/mL, MeOH). The HCl-salt was precipitated from diethyl ether at 0° C. and recrystallized from ethanol/diethyl ether. mp 159°-161° C. (dec).

Workup

  1. additionSome molcular sieves (3 Å) were added
  2. customThe solvent was removed in vacuo
  3. dissolutionThe residue was dissolved in methanol (30 mL) under nitrogen atmosphere
  4. waitthe reflux was continued for 3 hours
  5. waitthe reflux was continued for 12 hours
  6. customThe solvent was removed in vacuo
  7. dissolutionThe residue was dissolved in diethyl ether/2M NH3
  8. customThe layers were separated
  9. extractionthe water-phase was extracted once more with ether
  10. dry with materialdried (Na2SO4)
  11. customThe solvent was removed in vacuo
  12. customto give a brown oily residue which
  13. customwas purified by flash chromatography (SiO2, first CH2Cl2 /EtOAc, 5:1
  14. additionalso containing 0.5% of NH3

Sources & evidence

ORD record
ord-e86dae97e2e24583a5d5efbb3b020ab1
Source dataset
uspto-grants-1997_07
Patent number
US05650524

Reaction notes

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