4-Fluorobenzoic Acid → 4-Fluoro-N-methoxy-N-methylbenzamide

HRID 1038648Notes

Reaction equation

HRID 1038648 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1.CN([C:33]([O:37][N:38]1N=NC2C=CC=C[C:39]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.CNOC>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:38]([O:37][CH3:33])[CH3:39])=[O:7])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 99734-Fluorobenzoic AcidHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 140693474-Fluoro-N-methoxy-N-methylbenzamideYield 79%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-fluorobenzoic acid (6.8 g, 48.57 mmole) in 100 mL of DMF at room temperature, is added diisopropylethylamine (25.3 mL, 145.7 mmole). After stirring at room temperature for 20 minutes, HOBT (7.22 g, 53.43 mmole), HBTU (20.26 g, 53.43 mmole) and N,O-dimethyl hydroxylamine hydrochloride (5.69 g, 58.29 mmole) are added to the reaction solution. After stirring at room temperature for 2 hours, the reaction solution is diluted with 200 mL of EtOAc and washed with 4×50 mL of water. The combined organic layers is concentrated and purified by flash column chromatography (hexane 70%, EtOAc 30%) to yield 4-fluoro-N-methoxy-N-methyl-benzamide (4a) (7.0 g, yield 79%).

Workup

  1. stirringAfter stirring at room temperature for 2 hours
  2. washwashed with 4×50 mL of water
  3. concentrationThe combined organic layers is concentrated
  4. custompurified by flash column chromatography (hexane 70%, EtOAc 30%)

Sources & evidence

ORD record
ord-7ae5ac2eb3a641c893f872f41fce2fd1
Source dataset
uspto-grants-2013_10
Patent number
US08552003B2

Reaction notes

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