Dimethylformamide → 4-({[2-(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetyl]-methoxy-amino}-methyl)-n-methyl-benzamide

HRID 1836537Notes

Reaction equation

HRID 1836537 reaction equation
[CH3:1][C:2]1([CH3:24])[O:6][C:5](=[CH:7][C:8]([N:10]([CH2:13][C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)[O:11][CH3:12])=[O:9])[C:4](=[O:23])[O:3]1.C(Cl)(=O)C(Cl)=O.[CH3:31][N:32](C)C=O>ClCCl>[CH3:1][C:2]1([CH3:24])[O:6][C:5](=[CH:7][C:8]([N:10]([CH2:13][C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:32][CH3:31])=[O:19])=[CH:16][CH:15]=2)[O:11][CH3:12])=[O:9])[C:4](=[O:23])[O:3]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 738555554-({[2-(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetyl]-methoxy-amino}-methyl)-benzoic acid

Product 1

HCID 738555444-({[2-(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetyl]-methoxy-amino}-methyl)-n-methyl-benzamideYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-({[2-(2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetyl]-methoxy-amino}-methyl)-benzoic acid (0.150 g, 0.45 mmol) in dichloromethane (2 ml) was treated at 22° C. with oxalyl chloride (0.08 ml) and a trace (capillary) of N,N-dimethylformamide and the resulting mixture was stirred for 2 h. The solvent and excess reagent were evaporated in vacuo and the residue was dissolved in dichloromethane (2 ml). This solution was added dropwise to a cold (5° C.) solution of methylamine (0.5 mmol, 0.25 ml of a 2M solution in tetrahydrofuran) and pyridine (0.01 ml) in dichloromethane (2 ml). After 1 h at 22° C., the reaction mixture was diluted with ethyl acetate, washed successively with 0.1 N hydrochloric acid, saturated sodium bicarbonate, brine and dried over anhydrous magnesium sulphate. Evaporation of the solvent under reduced pressure and chromatography of the residue on silica gel (elution ethyl acetate and acetonitrile, 0 to 5%) yielded 0.060 g (38% yield) of the title amide as a white solid. 1HNMR 400 MHz (DMSO-d6) δ (ppm): 1.69 (6H, s, CH3), 2.77 (3H, d, J=4.5 Hz, NCH3), 3.72 (2H, s, OCH3), 4.85 (2H, s, NCH2), 6.18 (1H, s, CH), 7.35 (2H, d, J=8.2 Hz, aromatics), 7.79 (2H, d, J=8.2 Hz, aromatics), 8.41 (1H, broad q, NH).

Workup

  1. customThe solvent and excess reagent were evaporated in vacuo
  2. dissolutionthe residue was dissolved in dichloromethane (2 ml)
  3. additionThis solution was added dropwise to a cold (5° C.) solution of methylamine (0.5 mmol, 0.25 ml of a 2M solution in tetrahydrofuran) and pyridine (0.01 ml) in dichloromethane (2 ml)
  4. additionthe reaction mixture was diluted with ethyl acetate
  5. washwashed successively with 0.1 N hydrochloric acid, saturated sodium bicarbonate, brine
  6. dry with materialdried over anhydrous magnesium sulphate
  7. customEvaporation of the solvent under reduced pressure and chromatography of the residue on silica gel (elution ethyl acetate and acetonitrile, 0 to 5%)

Sources & evidence

ORD record
ord-21b5afb8afea4fa5a12ecd85230880a8
Source dataset
uspto-grants-2004_08
Patent number
US06777440B2

Reaction notes

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