Ammonia → 2-Amino-4,6-difluorobenzamide

HRID 1014165Notes

Reaction equation

HRID 1014165 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([F:12])[C:3]=1[C:4](O)=[O:5].CC[N:15]=C=NCCCN(C)C.Cl.Cl.C1C=CC2N(O)N=NC=2C=1.N>O1CCCC1.CN(C)C(=O)C>[NH2:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([F:12])[C:3]=1[C:4]([NH2:15])=[O:5]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 146519722-Amino-4,6-difluorobenzoic acid

Product 1

HCID 594419592-Amino-4,6-difluorobenzamideYield 78%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 2-amino-4,6-difluoro benzoic acid (4.0 g, 23.12 mmol, Butt Park Ltd.) in tetrahydrofuran (1.0 L) and N,N-dimethylacetamide (150 mL) was added EDCl.HCl (13.44 g, 70 mmol, Aldrich), HOBT (9.5 g, 70 mmol, Aldrich) and ammonia as a 0.5M solution in dioxanes (460 mL, 230 mmol, Aldrich). The resultant slurry was stirred for 24 hours, and then solids removed by filtration through celite. The filtrate was taken to a residue under reduced pressure and partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate, filtered, taken to a residue under reduced pressure, and purified by chromatography on SiO2 (Ethyl acetate/Hexanes) to afford analytically pure 2-amino-4,6-difluorobenzamide as a white crystalline solid (3.11 g, 78% yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 6.21-6.27 (m, 1 H), 6.27-6.32 (m, 1 H), 6.52 (s, 2 H), 7.48 (s, 1 H), 7.53 (s, 1 H).

Workup

  1. customsolids removed by filtration through celite
  2. custompartitioned between water and ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. custompurified by chromatography on SiO2 (Ethyl acetate/Hexanes)

Sources & evidence

ORD record
ord-92c0e411206243d39af761005438e30e
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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