2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl → HCID 56932932, compound

HRID 1972375Notes

Reaction equation

HRID 1972375 reaction equation
Cl.[CH3:2][C@H:3]1[CH2:8][N:7]([S:9]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)(=[O:11])=[O:10])[CH2:6][CH2:5][NH:4]1.Br[C:18]1[CH:23]=[CH:22][C:21]([C:24]([OH:30])([CH3:29])[C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>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].C1(C)C=CC=CC=1>[F:26][C:25]([F:27])([F:28])[C:24]([C:21]1[CH:20]=[CH:19][C:18]([N:4]2[CH2:5][CH2:6][N:7]([S:9]([C:12]3[S:13][CH:14]=[CH:15][CH:16]=3)(=[O:11])=[O:10])[CH2:8][C@@H:3]2[CH3:2])=[CH:23][CH:22]=1)([OH:30])[CH3:29]

Participants

8

Reactant 4

HCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 583472902-(4-Bromophenyl)-1,1,1-trifluoropropan-2-olHCID 66582368HCID 66582368, compound

Product 1

HCID 56932932HCID 56932932, compoundYield 85.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A 100 mL round-bottomed flask was charged with (S)-2-methyl-4-(2-thiophenylsulfonyl)piperazine hydrochloride (10.0 g, 35.4 mmol), 2-(4-bromophenyl)-1,1,1-trifluoro-2-propanol (16.7 g, 61.9 mmol, Example 27, step 1), sodium tert-butoxide (13.6 g, 141 mmol) and 20 mL of toluene. To this was added dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (RuPhos) (1.98 g, 4.24 mmol, Strem Chemical Inc, Newburyport, Mass.), tris(dibenzylideneacetone)dipalladium (0) (1.94 g, 0.265 mmol, Strem Chemical Inc, Newburyport, Mass.). The mixture was heated at 100° C. for 12 h. After that time, the reaction was diluted with water (100 mL) and extracted with EtOAc (2×150 mL). The combined extracts were dried (MgSO4) and concentrated and purified by column chromatography (330 g of silica, 0 to 50% EtOAc in hexanes) to give 1,1,1-trifluoro-2-(4-((2S)-2-methyl-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (13.20 g) as a mixture of two isomers.

Workup

  1. extractionextracted with EtOAc (2×150 mL)
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. concentrationconcentrated
  4. custompurified by column chromatography (330 g of silica, 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-62e5064f3b9949d696fcfc2714de0944
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

Loading…