2-(Tributylstannyl)-1,3-thiazole → 2-Fluoro-5-(1,3-thiazol-2-yl)pyridine

HRID 2205527Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.C([Sn](CCCC)(CCCC)[C:14]1[S:15][CH:16]=[CH:17][N:18]=1)CCC>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:8][C:5]1[N:6]=[CH:7][C:2]([C:14]2[S:15][CH:16]=[CH:17][N:18]=2)=[CH:3][CH:4]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 5-bromo-2-fluoropyridine (0.5 g, 2.857 mmol) in DMF (6 mL), 2-(tributylstannyl)thiazole (1.3 mL, 4.285 mmol) and Pd(PPh3)2Cl2(0.2 mg, 0.2857 mmol) were added under argon. The mixture was degassed with argon for 10 min and heated to 100° C. for 30 min. The reaction mixture was filtered through Celite® reagent and the filtrate was diluted with EtOAc (2×100 mL) and water (100 mL). The organic layer was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to obtain crude product. The crude product was purified by Biotage IsoleraOne® column (5% ethyl acetate in hexane) to obtain 2-(6-fluoropyridin-3-yl) thiazole as off-white solid (0.4 g, 80% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.80 (s, 1H), 8.52-8.47 (m, 1H), 7.98 (d, 1H), 7.87 (d, 1H), 7.33 (dd, 1H); LC-MS m/z calculated for [M+11]+181.02. found 180.8.

Workup

customThe mixture was degassed with argon for 10 min
filtrationThe reaction mixture was filtered through Celite® reagent
additionthe filtrate was diluted with EtOAc (2×100 mL) and water (100 mL)
customThe organic layer was separated
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customto obtain crude product
customThe crude product was purified by Biotage IsoleraOne® column (5% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-5e5aced18a164a34becc882ad83b16dd
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371316B2

Reaction notes

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