Pyridine → HCID 10465609, compound

HRID 1416363Notes

Reaction equation

HRID 1416363 reaction equation
[C:1]([CH2:5][C:6](Cl)=[O:7])([O:3][CH3:4])=[O:2].[CH3:9][NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.N1C=CC=CC=1>C(Cl)Cl>[CH3:9][N:10]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:6](=[O:7])[CH2:5][C:1]([O:3][CH3:4])=[O:2]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7515N-MethylanilineHCID 123460Methyl malonyl chloride

Product 1

HCID 10465609HCID 10465609, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The carbomethoxy acetyl chloride mixture is cooled in an ice-salt bath to -5 to 0° and N-methyl aniline (55.64 g, 0.52 mol) in methylene chloride (200 ml) is added at a rate so as to maintain the temperature of the reaction mixture between -5 to 0°. The addition is performed using an addition funnel and can normally be carried out over a 3-5 min time period to control the slight exotherm. Pyridine (66.36 g, 0.84 mol) in methylene chloride (200 ml) is then added to the above mixture. The addition rate is adjusted so as to keep the temperature of the reaction between -5 to 0° during the addition. The addition is performed using an addition funnel and can normally be carried out over a 3-5 min time period to control the slight exotherm. After the addition is complete (as measured by HPLC) the reaction is quenched by pouring the reaction mixture into water (500 ml) and stirring continued for 30 min. The reaction is equilibrated and the methylene chloride layer separated. Additional methylene chloride (400-500 ml) is added and the methylene chloride mixture is washed successively with hydrochloric acid (1N, 2×300 ml), saturated sodium bicarbonate solution (2×300 ml), saline (1×600 ml) and the methylene chloride mixture dried through anhydrous sodium sulfate. Concentration of the mixture under reduced pressure at 40-45° gives the title compound, HPLC (Nucleosil column; acetonitrile/water, 45/55, 1 ml/min, UV=229 nm; Retention times for N-methyl-N-phenyl-α-carbomethoxyacetamide~6.0 min; N-methyl aniline~11.0-12.0 min.

Workup

  1. temperatureto maintain the temperature of the reaction mixture between -5 to 0°
  2. additionThe addition
  3. customthe temperature of the reaction between -5 to 0°
  4. additionduring the addition
  5. additionThe addition
  6. waitcan normally be carried out over a 3-5 min
  7. additionAfter the addition
  8. customis quenched
  9. additionby pouring the reaction mixture into water (500 ml)
  10. waitcontinued for 30 min
  11. customthe methylene chloride layer separated
  12. additionAdditional methylene chloride (400-500 ml) is added
  13. washthe methylene chloride mixture is washed successively with hydrochloric acid (1N, 2×300 ml), saturated sodium bicarbonate solution (2×300 ml), saline (1×600 ml)
  14. dry with materialthe methylene chloride mixture dried through anhydrous sodium sulfate

Sources & evidence

ORD record
ord-bb1daa62387543a0a79a45fd51f088ff
Source dataset
uspto-grants-1999_06
Patent number
US05912349

Reaction notes

Loading…