2-(2,6-Dichloropyridin-3-yl)ethan-1-ol → 2-(6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)ethanol

HRID 595759Notes

Reaction equation

Cl[C:2]1[C:7]([CH2:8][CH2:9][OH:10])=[CH:6][CH:5]=[C:4]([Cl:11])[N:3]=1.[F:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[C:16](B1OC(C)(C)C(C)(C)O1)[NH:17]2>O1CCOCC1.O.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[Cl:11][C:4]1[N:3]=[C:2]([C:16]2[NH:17][C:18]3[C:14]([CH:15]=2)=[C:13]([F:12])[CH:21]=[CH:20][CH:19]=3)[C:7]([CH2:8][CH2:9][OH:10])=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a degassed solution of 2-(2,6-dichloropyridin-3-yl)ethanol (200 mg, 1.04 mmol) and 4-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (272 mg, 1.04 mmol) in 1,4-dioxane (8 mL) and water (200 μl) was added CS2CO3 (679 mg, 2.08 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium chloride (68 mg, 0.10 mmol) under N2 protection. The resulting mixture was heated to 90° C. and stirred at this temperature overnight. The reaction was cooled, filtered through a pad of the celite and washed with ethyl acetate. The combined filtrate was evaporated in vacuo. Preparative TLC (eluted with 20% EtOAc/DCM) to provide 2-(6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)ethanol (60 mg, yield: 19%) MS (M+H)+: 291.

Workup

temperatureThe reaction was cooled
filtrationfiltered through a pad of the celite
washwashed with ethyl acetate
customThe combined filtrate was evaporated in vacuo
washPreparative TLC (eluted with 20% EtOAc/DCM)

Sources & evidence

ORD record: ord-9ca8b0f56ba94f18afe857ef43b36649
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

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