2-Fluorobenzoyl chloride → Ataluren

HRID 28526

Reaction equation

HRID 28526 reaction equation
C[O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10](=[NH:13])[NH:11][OH:12])[CH:5]=1.C(N(C(C)C)CC)(C)C.[F:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27](Cl)=O>C1COCC1>[F:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27]1[O:12][N:11]=[C:10]([C:6]2[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=2)[C:3]([OH:2])=[O:14])[N:13]=1

Participants

5

Reactant 3

HCID 98082-Fluorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 178497860HCID 178497860, compound

Product 1

HCID 11219835AtalurenYield 91.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(N-Hydroxycarbamimidoyl)-benzoic acid methyl ester (60 g, 310 mmol) in anhydrous THF (200 mL) was added diisopropylethylamine (75 mL, 434 mmol) at 5° C., and then to the mixture was added 2-fluorobenzoyl chloride (48.1 mL, 403 mmol) over 20 min. The reaction mixture was stirred for 1 h at room temperature. The precipitate was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethylacetate (400 mL) and then washed with water (200 mL×2). The solvent was removed under reduced pressure and the desired product was crystallized in 60% ethylacetate in hexane to yield the desired product (81 g, 83% yield) as a white solid. 1H-NMR (CDCl3) δ 8.18 (1H), 8.03 (2H), 7.48 (2H), 7.18 (2H), 5.61 (2H), 3.82 (3H).

Workup

  1. filtrationThe precipitate was filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethylacetate (400 mL)
  4. washwashed with water (200 mL×2)
  5. customThe solvent was removed under reduced pressure
  6. customthe desired product was crystallized in 60% ethylacetate in hexane

Sources & evidence

ORD record
ord-3f5d44e8a9504472b926b1e23df66bc2
Source dataset
uspto-grants-2008_09
Patent number
US07419991B2

Linked notes

Loading…