Hydrochloric Acid → HCID 56932423, compound

HRID 1972462Notes

Reaction equation

HRID 1972462 reaction equation
C1(C(C2C=CC=CC=2)=[NH:8])C=CC=CC=1.Br[C:16]1[S:20][C:19]([S:21]([N:24]2[CH2:29][CH2:28][N:27]([C:30]3[CH:35]=[CH:34][C:33]([C:36]([OH:42])([CH3:41])[C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=3)[CH2:26][CH2:25]2)(=[O:23])=[O:22])=[CH:18][CH:17]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl.[OH-].[Na+]>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOCC.C1(C)C=CC=CC=1>[NH2:8][C:16]1[S:20][C:19]([S:21]([N:24]2[CH2:29][CH2:28][N:27]([C:30]3[CH:35]=[CH:34][C:33]([C:36]([OH:42])([CH3:41])[C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=3)[CH2:26][CH2:25]2)(=[O:23])=[O:22])=[CH:18][CH:17]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 66582557HCID 66582557, compound

Product 1

HCID 56932423HCID 56932423, compoundYield 48.1%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A 20-mL vial was charged with 1,1-diphenylmethanimine (0.44 g, 2.40 mmol), 2-(4-(4-((5-bromo-2-thiophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (1.00 g, 2.003 mmol), sodium tert-butoxide (0.46 mL, 4.81 mmol), and 10 mL of toluene. To this was added tris(dibenzylideneacetone)dipalladium (0) (0.18 g, 0.20 mmol, Strem Chemicals, Newburyport, Mass.) and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (0.31 g, 0.50 mmol, Sigma-Aldrich, St. Louis, Mo.). The vial was sealed and heated at 80° C. for 12 h. The mixture was then diluted with EtOAc (10 mL) and filtered. The filtrate was concentrated and the dissolved in 15 mL of THF. To this was added 5 M HCl (15.0 mL, 75 mmol). After stirring at room temperature for 30 min, the pH was adjusted to 12 by 5N NaOH. The mixture was extracted with EtOAc, dried with MgSO4, filtered, and concentrated. Purification via column chromatography on silica gel (0-70% EtOAc in hexanes) gave a white foam. To this was added 25 mL of ether and 25 mL of hexanes. The resulting suspension was stirred at room temperature for 5 min. The white solid was collected by filtration to give 2-(4-(4-((5-amino-2-thiophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.42 g).

Workup

  1. customThe vial was sealed
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. dissolutionthe dissolved in 15 mL of THF
  5. extractionThe mixture was extracted with EtOAc
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification via column chromatography on silica gel (0-70% EtOAc in hexanes)
  10. customgave a white foam
  11. stirringThe resulting suspension was stirred at room temperature for 5 min
  12. filtrationThe white solid was collected by filtration

Sources & evidence

ORD record
ord-f074a77136ce41fab5bad3c2f279b3e0
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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