Triethylamine → 2-fluoro-N,3-dimethoxy-N-methylbenzamide

HRID 2220333Notes

Reaction equation

HRID 2220333 reaction equation
[F:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.Cl.[CH3:54][NH:55][O:56][CH3:57]>C1COCC1.C(Cl)Cl>[F:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([N:55]([O:56][CH3:57])[CH3:54])=[O:6]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 2724699PyBOPHCID 33906792-Fluoro-3-methoxybenzoic acid

Product 1

HCID 179819292-fluoro-N,3-dimethoxy-N-methylbenzamideYield 37%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-fluoro-3-methoxy-benzoic acid (5.0 g, 29.4 mmol) and PyBOP (13.7 g, 29.4 mmol) in 7:1 CH2Cl2:THF was added triethylamine (4.10 mL, 29.4 mmol) over a 10 min period. N,O-Dimethylhydroxylamine hydrochloride (2.87 g, 29.4 mL) was then added and the reaction was allowed to stir at rt for 3 h. The reaction was then partitioned between dichloromethane and water. The organic phase was separated and the aqueous phase was extracted with 2×100 mL dichloromethane. The combined organic phases were dried (MgSO4) and concentrated in vacuo. The residue was taken up in ethyl acetate and was washed successively with 1N HCl, saturated aqueous NaHCO3, and brine. The organic phase was again dried (MgSO4) and concentrated in vacuo to yield the title compound (2.30 g, 37%).

Workup

  1. customThe reaction was then partitioned between dichloromethane and water
  2. customThe organic phase was separated
  3. extractionthe aqueous phase was extracted with 2×100 mL dichloromethane
  4. dry with materialThe combined organic phases were dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. washwas washed successively with 1N HCl, saturated aqueous NaHCO3, and brine
  7. dry with materialThe organic phase was again dried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4396e18ceaef4360959f6846f0879e56
Source dataset
uspto-grants-2008_08
Patent number
US07417064B2

Reaction notes

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