Hydrochloric Acid → 2-(3-Bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1-trifluoro-2-propanol

HRID 1972446Notes

Reaction equation

HRID 1972446 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([OH:14])([CH3:13])[C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[N:15]1[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]1.Cl.O1CCOCC1.C(N(CC)CC)C.[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[S:47](Cl)(=[O:49])=[O:48]>CCOC(C)=O>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([OH:14])([CH3:13])[C:9]([F:10])([F:12])[F:11])[CH:5]=[CH:4][C:3]=1[N:15]1[CH2:16][CH2:17][N:18]([S:47]([C:43]2[S:42][CH:46]=[CH:45][CH:44]=2)(=[O:49])=[O:48])[CH2:19][CH2:20]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 855182-Thiophenesulfonyl chlorideHCID 66582356Tert-butyl 4-(2-bromo-4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-1-piperazinecarboxylate

Product 1

HCID 665829132-(3-Bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1-trifluoro-2-propanolYield 67.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A 250 mL round-bottomed flask was charged with tert-butyl 4-(2-bromo-4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-1-piperazinecarboxylate (3.70 g, 8.16 mmol), 25 mL of EtOAc, and 8 mL of 4M HCl in dioxane (32 mmol). After heating at reflux for 30 min, the mixture was cooled and concentrated. The resulting viscous oil was dissolved in 30 mL of CH2Cl2 and triethylamine (3.98 mL, 28.6 mmol). At 0° C., 2-thiophenesulfonyl chloride (1.49 g, 8.16 mmol, Sigma-Aldrich, St. Louis, Mo.) was added at 0° C. After 15 min, the mixture was concentrated then re-dissolved in 5 mL of CH2Cl2, filtered, and purified via column chromatography (120 g of silica, 0 to 50% EtOAc in hexanes) to give 2-(3-bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1-trifluoro-2-propanol (2.75 g) as a white solid.

Workup

  1. temperatureAfter heating
  2. temperatureat reflux for 30 min
  3. temperaturethe mixture was cooled
  4. concentrationconcentrated
  5. dissolutionThe resulting viscous oil was dissolved in 30 mL of CH2Cl2
  6. concentrationthe mixture was concentrated
  7. dissolutionthen re-dissolved in 5 mL of CH2Cl2
  8. filtrationfiltered
  9. custompurified via column chromatography (120 g of silica, 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9550fbd33772405bbd691f43f9f7b2a4
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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