Ammonia → 2-Amino-4-chloro-6-fluorobenzamide

HRID 1014171Notes

Reaction equation

HRID 1014171 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[C:7]([F:12])[C:3]=1[C:4](O)=[O:5].CC[N:15]=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.N>O1CCCC1>[NH2:1][C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[C:7]([F:12])[C:3]=1[C:4]([NH2:15])=[O:5]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59441619940054-48-8

Product 1

HCID 594421282-Amino-4-chloro-6-fluorobenzamideYield 92.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-amino-4-chloro-6-fluorobenzoic acid (3.22 g, 17.04 mmol) in tetrahydrofuran (100 mL) was added EDCI.HCl (6.5 g, 34.1 mmol, Aldrich), HOBT (4.6 g, 34 mmol) and ammonia as a 0.5M solution in dioxanes (170 mL, 85 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-chloro-6-fluorobenzamide as a white crystalline solid (2.98 g, 92% Yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 6.40 (s, 2 H), 6.44 (dd, J=10.81, 2.02 Hz, 1 H), 6.57 (s, 1 H), 7.56 (s, 1 H), 7.60 (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-98923dfb0b6b429581c91298be632d21
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

Loading…