Tetrahydrofuran → 4-Benzo[b]thiophen-7-yl-2-fluoro-5-methyl-pyridine

HRID 1640913Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6](I)[C:5]([CH3:9])=[CH:4][N:3]=1.[S:10]1[CH:14]=[CH:13][C:12]2[CH:15]=[CH:16][CH:17]=[C:18](B3OC(C)(C)C(C)(C)O3)[C:11]1=2.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:10]1[CH:14]=[CH:13][C:12]2[CH:15]=[CH:16][CH:17]=[C:18]([C:6]3[C:5]([CH3:9])=[CH:4][N:3]=[C:2]([F:1])[CH:7]=3)[C:11]1=2

Participants

Conditions

Temperature: 100 °C

Procedure

In a flask, combine 2-fluoro-4-iodo-5-methyl-pyridine (355 mg, 1.5 mmol), 2-benzo[b]thiophen-7-yl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (282 mg, 1.8 mmol), Pd(dppf)Cl2 (61 mg, 0.07 mmol), 2-(di-tert-butylphos-phino)biphenyl (13 mg, 0.04 mmol), sodium carbonate (2 M, 1.5 mL, 3 mmol) and THF (10 mL). Heat the mixture at 100° C. for 3 h in an oil bath. Dilute the mixture with chloroform/IPA (3/1). Wash the solution with aqueous saturated sodium chloride. Dry over sodium sulfate. Concentrate in vacuo to a dark residue. Purify by column chromatography (20% ethyl acetate in hexane) to afford the title compound (300 mg, 82%) as a yellow oil. MS (ES) m/z 244 [M+1]+.

Workup

customIn a flask, combine
washWash the solution with aqueous saturated sodium chloride
dry with materialDry over sodium sulfate
concentrationConcentrate in vacuo to a dark residue
customPurify by column chromatography (20% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-babefff2256742279d84c585fac63b71
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08114872B2

Reaction notes

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