2-Fluorobenzoyl chloride → Ataluren

HRID 926685Notes

Reaction equation

HRID 926685 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

START HERE 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 forlh 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 (3H), 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-57f33ea8e6204c7ba748e888cdee4ae2
Source dataset
uspto-grants-2016_03
Patent number
US09289398B2

Reaction notes

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