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

HRID 4779

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

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

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

Sources & evidence

ORD record: ord-b0c0fc9ef6e847a68cadcb68fa16fa36
Source dataset: uspto-grants-1988_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04727152

Linked notes

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