Dimethylformamide → (2S)-5,5,5-trifluoro-2-({(1S)-2,2,2-trifluoro-1-[4'-(methylsulfonyl)-1,1'-biphenyl-4-yl]ethyl}amino)pentan-1-ol

HRID 2223545Notes

Reaction equation

HRID 2223545 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:13][C@@H:14]([CH2:17][CH2:18][C:19]([F:22])([F:21])[F:20])[CH2:15][OH:16])[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[CH3:23][S:24]([C:27]1[CH:32]=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=1)(=[O:26])=[O:25].CN(C=O)C>C(OCC)(=O)C.O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:20][C:19]([F:22])([F:21])[CH2:18][CH2:17][C@H:14]([NH:13][C@@H:8]([C:5]1[CH:6]=[CH:7][C:2]([C:30]2[CH:31]=[CH:32][C:27]([S:24]([CH3:23])(=[O:26])=[O:25])=[CH:28][CH:29]=2)=[CH:3][CH:4]=1)[C:9]([F:12])([F:11])[F:10])[CH2:15][OH:16]

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 27595302-(4-Methanesulfonylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86590545(2S)-2-{[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino}-5,5,5-trifluoropentan-1-ol

Product 1

HCID 86590548(2S)-5,5,5-trifluoro-2-({(1S)-2,2,2-trifluoro-1-[4'-(methylsulfonyl)-1,1'-biphenyl-4-yl]ethyl}amino)pentan-1-ol

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A stream of nitrogen was passed through a suspension of (2S)-2-{[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino}-5,5,5-trifluoropentan-1-ol (0.55 g), 2-(4-methanesulfonyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.59 g) 2.5 M K2CO3 (2.75 mL) and DMF (0.91 mL) for 20 minutes. [1,1′-Bis(diphenyl-phosphino)ferrocene]-palladium (II) chloride (1:1 complex with dichloromethane, 34 mg) was then added, the vessel sealed, and the reaction was warmed to 85° C. and stirred under nitrogen for 5 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL) and water (50 mL) and shaken vigorously. The ethyl acetate layer was separated and washed 3 times with water, dried with magnesium sulfate, and filtered. Removal of the solvent left a residue that was purified by chromatography on SiO2 using a gradient of 10-30% ethyl acetate in hexanes. Rotary evaporation of appropriate fractions yielded (2S)-5,5,5-trifluoro-2-({(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)pentan-1-ol.

Workup

  1. customthe vessel sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringshaken vigorously
  4. customThe ethyl acetate layer was separated
  5. washwashed 3 times with water
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. customRemoval of the solvent
  9. waitleft a residue that
  10. customwas purified by chromatography on SiO2 using a gradient of 10-30% ethyl acetate in hexanes
  11. customRotary evaporation of appropriate fractions

Sources & evidence

ORD record
ord-b6734aa74d154d64a2aa7b51dc053c66
Source dataset
uspto-grants-2008_05
Patent number
US07375134B2

Reaction notes

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