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 2425485Notes

Reaction equation

HRID 2425485 reaction equation
[CH3:1][N:2]([CH3:27])[C:3]([C:5]1[N:6]=[CH:7][C:8]([O:11][C:12]2[CH:13]=[C:14]([CH:19]=[C:20]([O:22][C@@H:23]([CH3:26])[CH2:24][OH:25])[CH:21]=2)[C:15]([O:17][CH3:18])=[O:16])=[N:9][CH:10]=1)=[O:4].[F:28][C:29]([F:37])(S(F)(=O)=O)C(O)=O>C(#N)C.[Cu]I>[F:28][CH:29]([F:37])[O:25][CH2:24][C@@H:23]([O:22][C:20]1[CH:19]=[C:14]([CH:13]=[C:12]([O:11][C:8]2[CH:7]=[N:6][C:5]([C:3](=[O:4])[N:2]([CH3:1])[CH3:27])=[CH:10][N:9]=2)[CH:21]=1)[C:15]([O:17][CH3:18])=[O:16])[CH3:26]

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-benzoate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
55 °C

Procedure

A solution of methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-hydroxypropan-2-yl]oxy-benzoate (94 g, 250 mmol) in acetonitrile (1130 mL) was degassed with nitrogen then copper(I) iodide (9.54 g, 50 mmol) was charged and the solution was heated to 55° C. A solution of 2,2-difluoro-2-fluorosulfonyl-acetic acid (CAS no. 1717-59-5) (46.6 mL, 450 mmol) in acetonitrile (188 mL) was charged dropwise. After 3 hours the solvent was evaporated under reduced pressure at 25° C. The residue was taken up in dichloromethane (500 mL) and filtered. The solid was washed further with dichloromethane until the washings were clear. The solvent was evaporated under reduced pressure at 25° C. and the residue was purified by flash chromatography eluting with 100% ethyl acetate to afford the title compound (54 g).

Workup

  1. customAfter 3 hours the solvent was evaporated under reduced pressure at 25° C
  2. filtrationfiltered
  3. washThe solid was washed further with dichloromethane until the washings
  4. customThe solvent was evaporated under reduced pressure at 25° C.
  5. customthe residue was purified by flash chromatography
  6. washeluting with 100% ethyl acetate

Sources & evidence

ORD record
ord-34576ba338f8449fa742843c267b8b19
Source dataset
uspto-grants-2011_06
Patent number
US07964725B2

Reaction notes

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