Cesium carbonate → HCID 86670329, compound

HRID 1972438Notes

Reaction equation

HRID 1972438 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:22]([OH:31])([C:27]([F:30])([F:29])[F:28])[C:23]([F:26])([F:25])[F:24])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)(=[O:16])=[O:15])[CH2:10][CH2:9]1.[C:32]1(B(O)[OH:39])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.O.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].Cl[Pd]Cl>[F:28][C:27]([F:30])([F:29])[C:22]([OH:31])=[O:39].[F:24][C:23]([F:26])([F:25])[C:22]([C:4]1[CH:3]=[C:2]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:7]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([C:17]3[S:18][CH:19]=[CH:20][CH:21]=3)(=[O:16])=[O:15])[CH2:10][CH2:9]2)=[CH:6][CH:5]=1)([OH:31])[C:27]([F:30])([F:29])[F:28]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 86670331HCID 86670331, compound

Product 1

HCID 86670329HCID 86670329, compoundYield 79.4%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

2-(3-bromo-4-(4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (90 mg, 0.163 mmol), phenylboronic acid (23.8 mg, 0.195 mmol, Sigma-Aldrich, St. Louis, Mo.), 1,1′ bis(diphenylphosphino)ferrocene]dichloropalladium (II) (13.28 mg, 0.016 mmol, Sigma-Aldrich, St. Louis, Mo.), and cesium carbonate (159 mg, 0.488 mmol) were combined in THF (3 mL) and water (1 mL). The reaction mixture was stirred and heated in a Discover model microwave reactor (CEM, Matthews, N.C.) at 100° C. for 10 min (100 watts, Powermax feature on, ramp time 5 min). The organic layer was separated and filtered through a PTFE (polytetrafluoroethylene) filter (0.45 micron). This crude material was subjected to reverse-phase preparative HPLC using a Phenomenex Gemini C18 column (150×30 mm, 10 μm) eluting with 0.1% TFA in CH3CN/H2O (10% to 90% over 20 min) to provide 1,1,1,3,3,3-hexafluoro-2-(6-(4-(2-thiophenylsulfonyl)-1-piperazinyl)-3-biphenylyl)-2-propanol trifluoroacetate (43 mg) as a tan oil. 1H NMR (300 MHz, CD3OD) δ 7.89 (d, J=4.8 Hz, 1H), 7.68-7.39 (m, 5H), 7.38-7.20 (m, 4H), 7.14 (d, J=8.6 Hz, 1H), 2.93 (br. s, 8H). m/z (ESI, +ve ion) 550.8 (M+H)+. GK-GKRP EC50 (NADPH-coupled)=2.12 μM; GK-GKRP EC50 (LC MS/MS)=1.75 μM.

Workup

  1. customThe organic layer was separated
  2. filtrationfiltered through a PTFE (polytetrafluoroethylene)
  3. filtrationfilter (0.45 micron)
  4. washeluting with 0.1% TFA in CH3CN/H2O (10% to 90% over 20 min)

Sources & evidence

ORD record
ord-162201836ea2412a824b1d8934115ea4
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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