Methylamine → HCID 22414390, compound

HRID 1721337Notes

Reaction equation

HRID 1721337 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([C:11]2[S:12][CH:13]=[CH:14][C:15]=2[CH3:16])=O)=[C:4]([N+:17]([O-:19])=[O:18])[CH:3]=1.[CH3:20][NH2:21]>C1(C)C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([C:11]2[S:12][CH:13]=[CH:14][C:15]=2[CH3:16])[NH:21][CH3:20])=[C:4]([N+:17]([O-:19])=[O:18])[CH:3]=1

Participants

5

Reactant 2

HCID 6329MethylamineHCID 10379793HCID 10379793, compound

Product 1

HCID 22414390HCID 22414390, compound

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
75 °C

Procedure

To a cooled (-60° C.) solution of 0.06 g of 2-(4-chloro-2-nitrophenyl)-1-(3-methyl-2-thienyl)ethanone in 270 ml of toluene, 70 ml of methylamine was added under a dry-ice-isopropanol condenser. The mixture was stirred for 0.5 hr. A solution of 4.6 ml of titanium tetrachloride in 46 ml of toluene was added dropwise. The dry-ice-isopropanol condenser was removed, a water condenser was attached, and the reaction was heated at an internal temperature of 75° C. for 2 hrs and stirred overnight at room temperature. The mixture was filtered and the filtrate was evaporated. To a solution of the residue in 250 ml of anhydrous methanol, ethereal hydrogen chloride was added dropwise until a pH of 3-5 was attained. A solution of 1.89 g of sodium cyanoborohydride in 25 ml of anhydrous methanol was added, and the mixture was stirred for 0.5 hr. An additional 1.0 g of sodium cyanoborohydride was added, and the mixture was stirred for one hr. The reaction was kept in the acidic pH range by periodic addition of ethereal hydrogen chloride. The solvent was evaporated, the residue was basified with 10% sodium hydroxide solution and extracted with ether. The combined extracts were washed with water, dried over anhydrous sodium sulfate, and concentrated. Purification was accomplished by preparative HPLC (Waters Associates Prep LC/System 500A, silica gel, 200 ml/min flow rate eluted with ethyl acetate and monitored by a Gow-Mac Model 80-800 uV detector. The appropriate fractions were collected and concentrated, and the residue was dissolved in ether and ethereal-hydrogen chloride was added to afford 5.6 g of product, mp 195°--197° C.

Workup

  1. additionwas added under a dry-ice-isopropanol condenser
  2. customThe dry-ice-isopropanol condenser was removed
  3. customa water condenser was attached
  4. stirringstirred overnight at room temperature
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated
  7. additionTo a solution of the residue in 250 ml of anhydrous methanol, ethereal hydrogen chloride was added dropwise until a pH of 3-5
  8. additionA solution of 1.89 g of sodium cyanoborohydride in 25 ml of anhydrous methanol was added
  9. stirringthe mixture was stirred for 0.5 hr
  10. additionAn additional 1.0 g of sodium cyanoborohydride was added
  11. stirringthe mixture was stirred for one hr
  12. additionThe reaction was kept in the acidic pH range by periodic addition of ethereal hydrogen chloride
  13. customThe solvent was evaporated
  14. extractionextracted with ether
  15. washThe combined extracts were washed with water
  16. dry with materialdried over anhydrous sodium sulfate
  17. concentrationconcentrated
  18. customPurification
  19. washeluted with ethyl acetate
  20. customThe appropriate fractions were collected
  21. concentrationconcentrated
  22. dissolutionthe residue was dissolved in ether
  23. additionethereal-hydrogen chloride was added

Sources & evidence

ORD record
ord-d8c26b1e81324681a595b67941b3bb68
Source dataset
uspto-grants-1996_04
Patent number
US05510346

Reaction notes

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