Nitrogen → 3-(4-Chloro-thiophen-2-yl)-pyridine

HRID 1432626Notes

Reaction equation

HRID 1432626 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([Cl:7])[CH:6]=1.[N:8]1[CH:13]=[CH:12][CH:11]=[C:10](B(O)O)[CH:9]=1.C([O-])([O-])=O.[Na+].[Na+].N#N.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2].C(O)CC>[Cl:7][C:5]1[CH:6]=[C:2]([C:10]2[CH:9]=[N:8][CH:13]=[CH:12][CH:11]=2)[S:3][CH:4]=1

Participants

9

Reactant 5

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27343783-Pyridinylboronic acidHCID 137808382-Bromo-4-chlorothiophene

Product 1

HCID 688427283-(4-Chloro-thiophen-2-yl)-pyridineYield 51.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 2-bromo-4-chloro-thiophene (Gronowitz, Rosén Chemica Scripta, 1971, 1, 33) (1.45 g, 7.34 mmol), pyridine-3-boronic acid (0.95 g, 7.71 mmol), 2 M Na2CO3 (5.50 mL, 11.01 mmol) and, n-PrOH (3 mL), is degassed with N2 for 10 minutes. Pd(OAc)2 (0.033 g, 0.15 mmol) and PPh3 (0.12 g, 0.44 mmol) are added and the solution is heated at 85° C. for 48 hours, diluted with CH2Cl2 (50 mL), washed with 10% Na2CO3 (2×30 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20%-30% EtOAc/hexane gradient) furnish the title compound (0.74 g, 3.78 mmol, 51%). 1H NMR (CDCl3), δ 7.12-7.13 (m, 1H), 7.20 (d, J=1.4 Hz, 1H), 7.31 (dd, J=8.0, 4.9 Hz, 1H), 7.78-7.82 (m, 1H), 8.55 (d, J=4.9 Hz, 1H), 8.82 (d, J=2.2 Hz, 1H).

Workup

  1. washwashed with 10% Na2CO3 (2×30 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO column chromatography (20%-30% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-1aeb054314434846a5bdc2fb3407d6a3
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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