Cesium carbonate → HCID 76462375, compound

HRID 1972517Notes

Reaction equation

HRID 1972517 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([Si](C)(C)[O:37][CH:38]([C:40]#[C:41]B1OC(C)(C)C(C)(C)O1)[CH3:39])(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.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]>[S:18]1[CH:19]=[CH:20][CH:21]=[C:17]1[S:14]([N:11]1[CH2:12][CH2:13][N:8]([C:7]2[CH:6]=[CH:5][C:4]([C:22]([OH:31])([C:27]([F:30])([F:29])[F:28])[C:23]([F:26])([F:25])[F:24])=[CH:3][C:2]=2[C:41]#[C:40][CH:38]([OH:37])[CH3:39])[CH2:9][CH2:10]1)(=[O:16])=[O:15]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 12174058tert-Butyl(dimethyl){[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-yn-2-yl]oxy}silaneHCID 86670331HCID 86670331, compound

Product 1

HCID 76462375HCID 76462375, compoundYield 23.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

2-(3-Bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (102 mg, 0.18 mmol, Example 69), tert-butyldimethyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-yn-2-yloxy)silane (86 mg, 0.28 mmol, Combi-Blocks, San Diego, Calif.), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride, dichloromethane complex (15 mg, 0.02 mmol, Sigma-Aldrich, St. Louis, Mo.), and cesium carbonate (180 mg, 0.55 mmol) were combined in DME (1.2 mL) and water (0.1 mL). The reaction mixture was purged with nitrogen for several minutes, and then stirred and heated in an Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 15 min and at 120° C. for 30 min. The reaction mixture was filtered through a pad of Celite® (diatomaceous earth) eluting with CH2Cl2 and the filtrate was concentrated in vacuo. The residue was suspended in 1N HCl (5 mL) and stirred at room temperature for 30 min. The mixture was partitioned between CH2Cl2 (5 mL) and saturated aqueous sodium bicarbonate (5 mL). The layers were separated, the organic material was dried (Na2SO4), filtered, and concentrated. The 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 (30% to 100% over 10 min) to provide 4-(2-(4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-3-butyn-2-ol (23 mg) as an off-white solid and a mixture of two enantiomers.

Workup

  1. customThe reaction mixture was purged with nitrogen for several minutes
  2. filtrationThe reaction mixture was filtered through a pad of Celite® (diatomaceous earth)
  3. washeluting with CH2Cl2
  4. concentrationthe filtrate was concentrated in vacuo
  5. stirringstirred at room temperature for 30 min
  6. customThe mixture was partitioned between CH2Cl2 (5 mL) and saturated aqueous sodium bicarbonate (5 mL)
  7. customThe layers were separated
  8. dry with materialthe organic material was dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. washeluting with 0.1% TFA in CH3CN/H2O (30% to 100% over 10 min)

Sources & evidence

ORD record
ord-6d707871d29b49808399104272913b0d
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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