2,2-Difluoro-2-(fluorosulfonyl)acetic acid → HCID 131733087, compound

HRID 1518969Notes

Reaction equation

HRID 1518969 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@H:10]([OH:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FS([C:26]([F:31])([F:30])C(O)=O)(=O)=O>C(#N)C.[Cu]I>[F:30][CH:26]([F:31])[O:21][C@H:10]1[C@H:11]([C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]1

Participants

5

Reactant 2

HCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 89555964HCID 89555964, compound

Product 1

HCID 131733087HCID 131733087, compoundYield 28.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
50 °C

Procedure

Dissolve trans-tert-butyl-4-(4-fluorophenyl)-3-hydroxy-piperidine-1-carboxylate (0.9 g, 3.1 mmol) and copper(I) iodide (116 mg, 609 mmol) in ACN (7.6 mL) and heat to 50° C. Add fluorosulfonyldifluoroacetic acid (336.7 mg, 1.83 mmol) dropwise over 15 minutes. Stir the solution for 2 hours at 50° C. and then cool to ambient temperature. Quench with a 50% solution of sodium bicarbonate; separate layers; and extract the aqueous layer twice with EtOAc. Combine the organic extracts; dry over sodium sulfate; filter; collect the filtrate; and concentrate under vacuum. Purify the crude material with silica gel flash column chromatography, with a gradient of 0-20% EtOAc in hexane to give the title compound (0.18 g, 17%). 1H-NMR (d6-DMSO) δ 0.74 (s, 1H), 1.42 (s, 9H), 1.5-1.79 (m, 2H), 2.6-2.85 (m, 2H), 3.59-4.82 (m, 4H), 6.4 (dd, J=76.8 Hz, 77.9 Hz, 1H), 7.0-7.1 (m, 2H), 7.27-7.33 (m, 2H).

Workup

  1. temperaturecool to ambient temperature
  2. customQuench with a 50% solution of sodium bicarbonate
  3. extractionand extract the aqueous layer twice with EtOAc
  4. dry with materialdry over sodium sulfate
  5. filtrationfilter
  6. customcollect the filtrate
  7. concentrationand concentrate under vacuum
  8. customPurify the crude material with silica gel flash column chromatography

Sources & evidence

ORD record
ord-2ac4a9a2046b485eba6d688295c70650
Source dataset
uspto-grants-2015_07
Patent number
US09073856B2

Reaction notes

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