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 2241936Notes

Reaction equation

HRID 2241936 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent2×

Procedure

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+)

Workup

  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

Sources & evidence

ORD record
ord-6c1a5a97902f4986bd9e22dd87610bae
Source dataset
uspto-grants-2010_03
Patent number
US07671060B2

Reaction notes

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