Salicylamide → 2-[(1-Methyl-3-pyrrolidinyl)oxy]benzamide

HRID 236121Notes

Reaction equation

HRID 236121 reaction equation
[NH2-].[Na+].[CH3:3][N:4]1[CH2:8][CH2:7][CH:6]([OH:9])[CH2:5]1.C1(C)C(S(Cl)(=O)=O)=CC=CC=1.C[O-].[Na+].[C:24]([NH2:33])(=[O:32])[C:25]1[C:26](=[CH:28][CH:29]=[CH:30][CH:31]=1)O>C1(C)C=CC=CC=1.CN(C)C=O>[CH3:3][N:4]1[CH2:8][CH2:7][CH:6]([O:9][C:31]2[CH:30]=[CH:29][CH:28]=[CH:26][C:25]=2[C:24]([NH2:33])=[O:32])[CH2:5]1

Participants

8

Reactant 5

HCID 5147SalicylamideHCID 8623o-Toluenesulfonyl chlorideHCID 24533Sodium amideHCID 930741-Methyl-3-pyrrolidinolHCID 10942334Sodium Methoxide

Product 1

HCID 137262832-[(1-Methyl-3-pyrrolidinyl)oxy]benzamide

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To 85.6 g (2.2 moles) of sodium amide in 1.5 liter of dry toluene was added 202 g (2 moles) of 1-methyl-3-pyrrolidinol so as not to exceed a temperature of 50° C. The mixture was then heated to 70° C. for 4.5 hours. The mixture was cooled and 381 g (2 moles) of o-toluenesulfonylchloride was added at a rapid drop while maintaining a temperature of 20°-30° C. with an ice bath. The mixture was stirred at room temperature for 2.5 hours and washed with water. The toluene solution was dried with sodium sulfate and concentrated. The residue, dissolved in 500 ml of dimethylformamide, was added to a reaction mixture prepared by adding 119 g (2.2 moles) of sodium methoxide and 274 g (2.0 moles) of salicylamide to one liter of dimethylformamide and the mixture was worked up as in preparation 1. Yield of product was 170 g (38%), m.p. 116°-118° C.

Workup

  1. customa temperature of 50° C
  2. temperatureThe mixture was cooled
  3. temperaturewhile maintaining a temperature of 20°-30° C. with an ice bath
  4. washwashed with water
  5. dry with materialThe toluene solution was dried with sodium sulfate
  6. concentrationconcentrated
  7. dissolutionThe residue, dissolved in 500 ml of dimethylformamide
  8. additionwas added to a reaction mixture
  9. customprepared
  10. customthe mixture was worked up as in preparation 1

Sources & evidence

ORD record
ord-233cc87da07d4246a5e14925e78a594b
Source dataset
uspto-grants-1987_02
Patent number
US04642343

Reaction notes

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