1,4-Dioxane → 7-Chloro-3-(4-fluorophenyl)thieno[3,2-b]pyridine

HRID 593768Notes

Reaction equation

Br[C:2]1[C:6]2=[N:7][CH:8]=[CH:9][C:10]([Cl:11])=[C:5]2[S:4][CH:3]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.O1CCOCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.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(Cl)Cl>[Cl:11][C:10]1[CH:9]=[CH:8][N:7]=[C:6]2[C:2]([C:16]3[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=3)=[CH:3][S:4][C:5]=12

Participants

Conditions

Temperature: 90 °C

Procedure

A vessel capable of sealing was charged with a mixture of 3-bromo-7-chlorothieno[3,2-b]pyridine (500 mg, 2.012 mmol), 4-fluorophenylboronic acid (310 mg, 2.213 mmol), PdCl2(dppf)-CH2Cl2 adduct (82 mg, 0.101 mmol), dioxane (8 mL), and a 2.0 M aqueous solution of K3PO4 (3 mL, 6.04 mmol) and was purged with nitrogen for 10 min. The vessel was sealed and heated at 90° C. for 1 h. Upon cooling, the reaction mixture was diluted with water and extracted with CH2Cl2. The combined organics were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude material was purified by BIOTAGE® eluting with 40%-80% EtOAc/CH2Cl2 at 30 mL/min. Concentration of appropriate fractions provided the title compound (450 mg, 49% yield) as a white powder. LC/MS: Example 98A @ 3.62 min (RT) (Condition G). MS (ES): m/z=263.03, [M+H]+.

Workup

customThe vessel was sealed
temperatureUpon cooling
extractionextracted with CH2Cl2
washThe combined organics were washed with brine
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated under reduced pressure
customThe crude material was purified by BIOTAGE®
washeluting with 40%-80% EtOAc/CH2Cl2 at 30 mL/min

Sources & evidence

ORD record: ord-31fa6e13f2954e0b95da59d815679d06
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242967B2

Reaction notes

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