Cesium carbonate → 6-Chloro-4'-(ethylsulfonyl)-2'-methoxy-[1,1'-biphenyl]-3-ol

HRID 1846034Notes

Reaction equation

HRID 1846034 reaction equation
C([Si]([O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[C:11](I)[CH:10]=1)(C)C)(C)(C)C.[CH2:17]([S:19]([C:22]1[CH:27]=[CH:26][C:25](B2OC(C)(C)C(C)(C)O2)=[C:24]([O:37][CH3:38])[CH:23]=1)(=[O:21])=[O:20])[CH3:18].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[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]>[Cl:15][C:12]1[C:11]([C:25]2[CH:26]=[CH:27][C:22]([S:19]([CH2:17][CH3:18])(=[O:21])=[O:20])=[CH:23][C:24]=2[O:37][CH3:38])=[CH:10][C:9]([OH:8])=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 867232082-(4-(Ethylsulfonyl)-2-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86723256tert-Butyl(4-chloro-3-iodophenoxy)dimethylsilane

Product 1

HCID 867232576-Chloro-4'-(ethylsulfonyl)-2'-methoxy-[1,1'-biphenyl]-3-olYield 72%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of tert-butyl(4-chloro-3-iodophenoxy)dimethylsilane (Preparation 53, 102 mg, 0.28 mmol), 2-(4-(ethylsulfonyl)-2-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Preparation 21) (90 mg, 0.28 mmol) and aqueous caesium carbonate solution (1M, 0.55 mL, 0.55 mmol) in dioxane (4 mL) was degassed with nitrogen for 10 minutes, followed by the addition of 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride (11.0 mg, 0.014 mmol). The resulting mixture was heated at 100° C. for 3 hours and then cooled to room temperature. The mixture was partitioned between water (15 mL) and EtOAc (15 mL), the aqueous layer then extracted with EtOAc (2×15 mL). The organic layers were combined and washed with brine (25 mL), dried over MgSO4 and then concentrated in vacuo. 4M HCl in dioxane (4 mL) was added to the residue, and the mixture stirred at room temperature for 40 hours. After concentration in vacuo, NH3 solution (7M in MeOH, 2 mL) was added to the residue, and the mixture re-concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with cyclohexane/EtOAc 70:30 to afford the title compound as yellow gum in 72% yield, 65 mg.

Workup

  1. temperaturecooled to room temperature
  2. customThe mixture was partitioned between water (15 mL) and EtOAc (15 mL)
  3. extractionthe aqueous layer then extracted with EtOAc (2×15 mL)
  4. washwashed with brine (25 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. addition4M HCl in dioxane (4 mL) was added to the residue
  8. concentrationAfter concentration in vacuo, NH3 solution (7M in MeOH, 2 mL)
  9. additionwas added to the residue
  10. concentrationthe mixture re-concentrated in vacuo
  11. customThe residue was purified by silica gel column chromatography
  12. washeluting with cyclohexane/EtOAc 70:30

Sources & evidence

ORD record
ord-3ea84e7ee23444199c742995855f39ce
Source dataset
uspto-grants-2015_02
Patent number
US08952008B2

Reaction notes

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