Methanol → N-methyl-2-(2-hydroxyphenyl)-2-methoxyiminoacetamide

HRID 432059Notes

Reaction equation

HRID 432059 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[N:13][O:14][CH3:15])[C:9](OC)=[O:10].OC1C=CC=CC=1/[C:23](=[N:28]/OC)/C(OC)=O.CN.CO>O1CCCC1>[CH3:23][NH:28][C:9](=[O:10])[C:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[OH:1])=[N:13][O:14][CH3:15]

Participants

6

Reactant 4

HCID 887MethanolHCID 6329Methylamine2×HCID 135424589methyl E-2-(2-hydroxyphenyl)-2-methoxyimino-acetateHCID 136127060HCID 136127060, compound

Product 1

HCID 136045378N-methyl-2-(2-hydroxyphenyl)-2-methoxyiminoacetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

0.5 g (0.0013 mol) of methyl 2-(2-hydroxyphenyl)-2-methoxyimino-acetate (in particular Example II-Id from process step 4; HPLC: 54.4% methyl Z-2-(2-hydroxyphenyl)-2-methoxyimino-acetate of log p=2.39 is disolved in 6 ml of tetrahydrofuran and cooled to 10° C. With cooling, methylamine is introduced. After about 30 minutes, 2 ml of methanol are added, the solution is saturated with methylamine and the mixture is allowed to stand at 10° C. overnight. The solvents are distilled off under reduced pressure and the residue is mixed with a mixture of 5 ml of 2 N hydrochloric acid and 5 ml of saturated sodium chloride solution and extracted three times with 10 ml of ethyl acetate each time. The organic phase is dried over sodium sulphate and the solvent is distilled off under reduced pressure, giving 0.6 g of crude product. This crude product is chromatographed with a mixture of 7 parts of n-hexane and 3 parts of acetone on silica gel. This gives 0.4 g of product which, according to HPLC, contains 99.2% N-methyl-Z-2-(2-hydroxyphenyl)-2-methoxyiminoacetamide of log p=1.29.

Workup

  1. temperatureWith cooling
  2. waitto stand at 10° C. overnight
  3. distillationThe solvents are distilled off under reduced pressure
  4. additionthe residue is mixed with a mixture of 5 ml of 2 N hydrochloric acid and 5 ml of saturated sodium chloride solution
  5. extractionextracted three times with 10 ml of ethyl acetate each time
  6. dry with materialThe organic phase is dried over sodium sulphate
  7. distillationthe solvent is distilled off under reduced pressure

Sources & evidence

ORD record
ord-82ee7253664048e88ba1ff2cea2b10f6
Source dataset
uspto-grants-2003_12
Patent number
US06660872B1

Reaction notes

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