Tetrahydrofuran → 4-Benzo[b]thiophen-7-yl-2-chloro-pyridine

HRID 1640912Notes

Reaction equation

HRID 1640912 reaction equation
Br[C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[Cl:11][C:12]1[CH:17]=[C:16](B2OC(C)(C)C(C)(C)O2)[CH:15]=[CH:14][N:13]=1.C(=O)([O-])[O-].[Na+].[Na+].C1COCC1>C(Cl)(Cl)Cl.C(O)(C)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>[S:8]1[CH:9]=[CH:10][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:16]3[CH:15]=[CH:14][N:13]=[C:12]([Cl:11])[CH:17]=3)[C:7]1=2

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 51034082-Chloropyridine-4-boronic acid, pinacol esterHCID 120455387-Bromobenzo[b]thiophene

Product 1

HCID 866402544-Benzo[b]thiophen-7-yl-2-chloro-pyridineYield 66.3%

Reagents, catalysts & solvents 3

HCID 27342152-(Di-tert-butylphosphino)biphenylCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21906603Chloroform isopropyl alcoholSolvent

Conditions

Temperature
100 °C

Procedure

In a flask, combine 7-bromo-benzo[b]thiophene (1.7 g, 12 mmol), 2-chloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (1.6 g, 7 mmol), Pd(dppf)Cl2 (285 mg, 0.3 mmol), 2-(di-tert-butylphosphino)biphenyl (63 mg, 0.2 mmol), sodium carbonate (2 M, 8 mL, 16 mmol) and THF (20 mL). Heat the mixture at 100° C. for 3 h. Dilute the mixture with chloroform/IPA (3/1). Wash the solution with aqueous saturated sodium chloride. Dry over sodium sulfate. Concentrate the solution in vacuo to a dark residue. Purify by column chromatography (DCM to 20% THF in DCM) to afford the title compound (1.14 g, 66%) as a yellow solid. MS (ES) m/z 246 [M+1]+.

Workup

  1. customIn a flask, combine
  2. washWash the solution with aqueous saturated sodium chloride
  3. dry with materialDry over sodium sulfate
  4. concentrationConcentrate the solution in vacuo to a dark residue
  5. customPurify by column chromatography (DCM to 20% THF in DCM)

Sources & evidence

ORD record
ord-d1394a0946dd492a956a84ffc57a09ec
Source dataset
uspto-grants-2012_02
Patent number
US08114872B2

Reaction notes

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