N,O-Dimethylhydroxylamine → 4,5-dichloro-2-fluoro-N-methoxy-N-methyl-benzamide

HRID 515085Notes

Reaction equation

HRID 515085 reaction equation
[Cl:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([F:12])[CH:3]=1.CN([C:16]([O:20][N:21]1N=NC2C=CC=N[C:22]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CONC.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)C>[Cl:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([N:21]([O:20][CH3:16])[CH3:22])=[O:7])=[C:4]([F:12])[CH:3]=1

Participants

7

Reactant 4

HCID 14232N,O-DimethylhydroxylamineHCID 81531DiisopropylethylamineHCID 27740154,5-Dichloro-2-fluorobenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 903153424,5-dichloro-2-fluoro-N-methoxy-N-methyl-benzamideYield 83%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

4,5-Dichloro-2-fluoro-benzoic acid (50 mg, 0.24 mmol), HATU (100.0 mg, 0.26 mmol) and N-methoxymethanamine (hydrochloric acid) (23.33 mg, 0.24 mmol) were combined in DMF (1.0 mL) and treated with DIEA (83.33 μL, 0.48 mmol). After 10 min, the reaction was complete. The reaction was diluted with diethyl ether and washed with 50% sat. NaHCO3 (2×) and brine, dried over Na2SO4, filtered and concentrated. Silica gel chromatography using a gradient of ethyl acetate/hexanes from 0 to 30% provided 4,5-dichloro-2-fluoro-N-methoxy-N-methyl-benzamide (50 mg, 83%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J=6.3 Hz, 1H), 7.26 (d, J=8.6 Hz, 1H), 3.56 (s, 3H), 3.35 (s, 3H) ppm.

Workup

  1. washwashed with 50% sat. NaHCO3 (2×) and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-1952eaada2ee417185d15f78894012c8
Source dataset
uspto-grants-2015_08
Patent number
US09108903B2

Reaction notes

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