2,2-Difluoro-2-(fluorosulfonyl)acetic acid → Methyl 3-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-benzoate

HRID 2241936Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2241936
[F:1][C:2]([F:10])(S(F)(=O)=O)C(O)=O.[CH3:11][N:12]([CH3:37])[C:13]([C:15]1[N:16]=[CH:17][C:18]([O:21][C:22]2[CH:23]=[C:24]([CH:29]=[C:30]([O:32][C@@H:33]([CH3:36])[CH2:34][OH:35])[CH:31]=2)[C:25]([O:27][CH3:28])=[O:26])=[N:19][CH:20]=1)=[O:14]>C(#N)C.[Cu]I>[F:1][CH:2]([F:10])[O:35][CH2:34][C@@H:33]([O:32][C:30]1[CH:29]=[C:24]([CH:23]=[C:22]([O:21][C:18]2[CH:17]=[N:16][C:15]([C:13](=[O:14])[N:12]([CH3:11])[CH3:37])=[CH:20][N:19]=2)[CH:31]=1)[C:25]([O:27][CH3:28])=[O:26])[CH3:36]

Komponenten

5

Edukt 2

HCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 59205095methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-hydroxypropan-2-yl]oxy-benzoate

Produkt 1

HCID 59205092Methyl 3-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-benzoateAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 6342AcetonitrileLösungsmittel2×

Versuchsvorschrift

2,2-Difluoro-2-fluorosulfonyl-acetic acid (CAS no. 1717-59-5) (0.84 mL, 8.05 mmol) in acetonitrile (20 mL) was added with a syringe pump dropwise over 90 minutes to a degassed stirring mixture of methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-hydroxypropan-2-yl]oxy-benzoate (1.5 g, 22.0 mmol) and copper (I) iodide (154 mg, 4.55 mmol) in acetonitrile (300 mL) at 55° C. The volatiles were removed under reduced pressure and the residue taken up in DCM. The mixture was filtered to and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica, eluting with a gradient of 25%-100% ethyl acetate in isohexane to afford the product (16.5 g, 62%). 1H NMR δ (CDCl3): 1.38 (3H, d), 3.15 (3H, s), 3.18 (3H, s), 3.91 (3H, s), 3.93-4.05 (2H, m), 4.62-4.68 (1H, m), 6.27 (1H, t), 6.95 (1H, t), 7.44-7.45 (1H, m), 7.49-7.51 (1H, m), 8.36 (1H, s), 8.53 (1H, s); m/z 404 (M+H+)

Aufarbeitung

  1. customThe volatiles were removed under reduced pressure
  2. filtrationThe mixture was filtered to and the solvent
  3. customwas removed under reduced pressure
  4. customThe residue was purified by flash chromatography on silica
  5. washeluting with a gradient of 25%-100% ethyl acetate in isohexane

Quellen und Nachweise

ORD-Eintrag
ord-6c1a5a97902f4986bd9e22dd87610bae
Quelldatensatz
uspto-grants-2010_03
Patentnummer
US07671060B2

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