2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl → 2-(4-((2S)-2-methyl-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-3,3,3-trifluoro-1,2-propanediol

HRID 1972436Notes

Reaction equation

HRID 1972436 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:15])([C:11]([F:14])([F:13])[F:12])[CH2:9][OH:10])=[CH:4][CH:3]=1.[CH3:16][C@@H:17]1[NH:22][CH2:21][CH2:20][N:19]([S:23]([C:26]2[S:27][CH:28]=[CH:29][CH:30]=2)(=[O:25])=[O:24])[CH2:18]1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>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].C1(C)C=CC=CC=1>[CH3:16][C@H:17]1[CH2:18][N:19]([S:23]([C:26]2[S:27][CH:28]=[CH:29][CH:30]=2)(=[O:25])=[O:24])[CH2:20][CH2:21][N:22]1[C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:15])([C:11]([F:14])([F:13])[F:12])[CH2:9][OH:10])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 66582369(3S)-3-methyl-1-(2-thiophenylsulfonyl)piperazineHCID 665825852-(4-Bromophenyl)-3,3,3-trifluoro-1,2-propanediol

Product 1

HCID 569323202-(4-((2S)-2-methyl-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-3,3,3-trifluoro-1,2-propanediolYield 4.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

2-(4-bromophenyl)-3,3,3-trifluoro-1,2-propanediol (0.35 g, 1.2 mmol), (3S)-3-methyl-1-(2-thiophenylsulfonyl)piperazine (0.20 g, 0.81 mmol), sodium tert-butoxide (0.27 g, 2.8 mmol), dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (RuPhos) (0.076 g, 0.16 mmol, Strem Chemical Inc, Newburyport, Mass.), tris(dibenzylideneacetone)dipalladium (0) (0.074 g, 0.081 mmol, Strem Chemical Inc, Newburyport, Mass.), and toluene (3.3 mL) were added to a high-pressure reaction vessel. The vessel was sealed and heated at 100° C. for 24 h. After cooling to room temperature, was purified via flash chromatography on silica gel (twice, 2% MeOH in CH2Cl2 then 33% EtOAc in hexanes) to afford 2-(4-((2S)-2-methyl-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-3,3,3-trifluoro-1,2-propanediol (0.017 g) as a mixture of two isomers.

Workup

  1. customThe vessel was sealed
  2. temperatureAfter cooling to room temperature
  3. customwas purified via flash chromatography on silica gel (twice, 2% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-969fe8159f6749229ba5ad83fd8a305e
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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