2,2-Difluoro-2-(fluorosulfonyl)acetic acid → HCID 118272222, compound

HRID 588157Notes

Reaction equation

HRID 588157 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([O:30][CH2:31][CH2:32][OH:33])=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.[F:34][C:35]([F:43])(S(F)(=O)=O)C(O)=O>C(#N)C.[Cu]I>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([O:30][CH2:31][CH2:32][O:33][CH:35]([F:43])[F:34])=[N:9][N:10]([C:11]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:4]=2[CH:3]=1

Participants

5

Reactant 2

HCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 118272021HCID 118272021, compound

Product 1

HCID 118272222HCID 118272222, compoundYield 55.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

A mixture of 2-((6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)oxy)ethanol (58B, 500 mg, 0.987 mmol) and copper(I) iodide (282 mg, 1.480 mmol) in acetonitrile (2861 μl) were degassed (evacuated and back filled w/Argon). 2,2-difluoro-2-(fluorosulfonyl)acetic acid (153 μl, 1.480 mmol) was added, degassed, and heated at 80° C. for 30 min. Reaction was quenched with water (1 mL), diluted with EtOAc and filtered through a celite pug. The solution was concentrated in vacuo on silica. Material was purified by normal phase column chromotography eluting with Hex/EtOAc (0-20%) affording 6-chloro-3-(2-(difluoromethoxy)ethoxy)-1-trityl-1H-pyrazolo[4,3-c]pyridine (59B, 277 mg, 0.547 mmol, 55.5% yield) as a white crystalline solid. MS: [M+H]+ m/z 506.

Workup

  1. customwere degassed (
  2. customevacuated
  3. additionback filled w/Argon)
  4. customdegassed
  5. customReaction
  6. customwas quenched with water (1 mL)
  7. additiondiluted with EtOAc
  8. filtrationfiltered through a celite pug
  9. concentrationThe solution was concentrated in vacuo on silica
  10. customMaterial was purified by normal phase column chromotography
  11. washeluting with Hex/EtOAc (0-20%)

Sources & evidence

ORD record
ord-1b97f2c474314548aee83dfa05c6f91b
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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