Water → 3,4-Dichloro-N-methoxy-N-methylbenzamide

HRID 2376251Notes

Reaction equation

HRID 2376251 reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].[Cl:6][C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[Cl:16])[C:10](Cl)=[O:11].CCN(C(C)C)C(C)C.O>CCOC(C)=O>[Cl:6][C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[Cl:16])[C:10]([N:3]([O:4][CH3:5])[CH3:2])=[O:11]

Participants

6

Reactant 4

HCID 962WaterHCID 76403Benzoyl chloride, 3,4-dichloro-HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531Diisopropylethylamine

Product 1

HCID 114136423,4-Dichloro-N-methoxy-N-methylbenzamideYield 107.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
35 °C

Procedure

N,O-Dimethylhydroxylamine hydrochloride (1.48 kg, 14.9 mol) was suspended in EtOAc (16 L) and warmed to 35° C. A solution of 3,4-dichlorobenzoyl chloride (3.00 kg, 13.9 mol) in EtOAc (8 L) was added, followed by addition of DIPEA (5.45 ml, 31.2 mol) while maintaining the temperature below 40° C. The reaction suspension was stirred for 1 h. When TLC analysis confirmed reaction completion by the disappearance of starting material, the reaction mixture was cooled to rt and H2O (10 L) was added to achieve a clear, biphasic solution. After removing the aqueous layer, the organic layer was dried (Na2SO4) and concentrated to afford the title compound (3.49 kg, 100%) as an oil. Upon sitting at rt, the product crystallized. IR (KBr pellet): 3445, 3258, 3091.6, 2981.4, 2945.5, 1942.4, 1645.6, 1588.6, 1557.4, 1462.9, 1414.5, 1368, 1386.2,1262, 1209, 1130, 1112.5, 1071.8, 1030.9, 100.9, 893.8. MS (ES+): mass calculated for C9H9Cl2NO2, 233.00; m/z found 234.0 [M+H]+. Mp: 39.5-43.2° C. 1H NMR (400 MHz, CDCl3): 7.80 (d, J=2 Hz, 1H), 7.54 (dd, J=8.4, 2.0 Hz, 1H), 7.46 (d, J=8.3 Hz, 1H), 3.54 (s, 3H), 3.34 (s, 3H). 13C NMR (100 MHz, CDCl3): 167.2, 135.0, 133.9, 132.4, 130.7, 130.2, 127.9, 61.5, 33.7.

Workup

  1. temperaturewhile maintaining the temperature below 40° C
  2. customreaction completion by the disappearance of starting material
  3. temperaturethe reaction mixture was cooled to rt
  4. customAfter removing the aqueous layer
  5. dry with materialthe organic layer was dried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-06b452bdfb5b495db4ebb30f98167c1d
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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