Hexane → 4-chloro-N-methoxy-N-methyl-2-phenylamino-benzamide

HRID 1887779

Reaction equation

HRID 1887779 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:3]=1.Cl.[CH3:19][NH:20][O:21][CH3:22].C(N(CC)C(C)C)(C)C.CCCCCC>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:20]([O:21][CH3:22])[CH3:19])=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 6153344-Chloro-2-(phenylamino)benzoic acid

Product 1

HCID 866720574-chloro-N-methoxy-N-methyl-2-phenylamino-benzamideYield 56.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 4-chloro-2-phenylamino-benzoic acid (10.1 g, 41.0 mmol) in DMF (200 mL) was added O-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluorophosphate (HBTU, 31.2 g, 82.0 mmol), N,O-dimethyl-hydroxylamine hydrochloride (7.94 g, 82.0 mmol), and N,N-diisopropylethylamine (45.0 g, 350.0 mmol) at room temperature. The resulting mixture was stirred for 24 hr. at room temperature. Completion of the reaction was confirmed by silica TLC (mobile phase; hexane:ethyl acetate=7:3; Rf=0.5). The reaction mixture was diluted with ethyl acetate (600 mL) and the organic layer was washed with water (4×200 mL) and brine (200 mL). The organic layer was dried over anhydrous Na2SO4 and volatiles were removed under reduced pressure. The crude material was purified over silica gel (100-200 mesh) column chromatography, using gradient polarity mobile phase (ethyl acetate:hexane=1:9-1:4), to give 4-chloro-N-methoxy-N-methyl-2-phenylamino-benzamide (6.62 g, 56.4% yield) as a yellow solid. 1H NMR (DMSO-d6) δ ppm 7.93 (s, 1H) 7.20-7.39 (m, 3H) 7.02-7.17 (m, 3H) 6.88-6.99 (m, 2H) 3.50 (s, 3H) 3.20 (s, 3H). MS calcd. for C15H15ClN2O2 [(M+H)+] 291.0, obsd. 291.0, [(M-C2H6NO)+] 230.0, obsd. 230.0.

Workup

  1. customat room temperature
  2. washthe organic layer was washed with water (4×200 mL) and brine (200 mL)
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4 and volatiles
  4. customwere removed under reduced pressure
  5. customThe crude material was purified over silica gel (100-200 mesh) column chromatography

Sources & evidence

ORD record
ord-1ba02ab243e74bb29276d331981087c3
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Linked notes

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