Triethylamine → 2-(4-(4-((2,6-Dichloropyridin-3-yl)sulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972537Notes

Reaction equation

HRID 1972537 reaction equation
Cl.Cl.[F:3][C:4]([F:24])([F:23])[C:5]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[CH:13][CH:12]=1)([OH:10])[C:6]([F:9])([F:8])[F:7].C(N(CC)CC)C.[Cl:32][C:33]1[C:38]([S:39](Cl)(=[O:41])=[O:40])=[CH:37][CH:36]=[C:35]([Cl:43])[N:34]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:32][C:33]1[C:38]([S:39]([N:20]2[CH2:21][CH2:22][N:17]([C:14]3[CH:13]=[CH:12][C:11]([C:5]([OH:10])([C:6]([F:9])([F:8])[F:7])[C:4]([F:3])([F:23])[F:24])=[CH:16][CH:15]=3)[CH2:18][CH2:19]2)(=[O:41])=[O:40])=[CH:37][CH:36]=[C:35]([Cl:43])[N:34]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 193787122,6-Dichloropyridine-3-sulfonyl chlorideHCID 866703461,1,1,3,3,3-Hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride

Product 1

HCID 866703912-(4-(4-((2,6-Dichloropyridin-3-yl)sulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanolYield 79.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a 20-mL vial was added 1,1,1,3,3,3-hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride (0.40 g, 1.0 mmol, Example 91), CH2Cl2 (8 mL), and triethylamine (0.70 mL, 5.0 mmol). To this solution was added 2,6-dichloropyridine-3-sulfonyl chloride (0.30 g, 1.2 mmol, Organic Process Research and Development 2009, 875). After stirring overnight at room temperature, saturated aqueous sodium bicarbonate and CH2Cl2 were added to the reaction mixture. After stirring for 5 min, the solution was transferred onto a phase separation cartridge (Radleys Discovery Technologies, Essex, UK) with the organic phase being collected and passed through a plug of Na2SO4. The collected solution was purified by silica gel chromatography (0 to 70% EtOAc in hexanes) to afford 2-(4-(4-((2,6-dichloropyridin-3-yl)sulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.43 g) as an off-white solid.

Workup

  1. stirringAfter stirring for 5 min
  2. customthe solution was transferred onto a phase separation cartridge (Radleys Discovery Technologies, Essex, UK) with the organic phase
  3. custombeing collected
  4. customThe collected solution was purified by silica gel chromatography (0 to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d3a99f362fe942928d63f51df28559ef
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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