Tetrahydrofuran → 2-(4-Chloro-6-(p-tolyl)pyridin-2-yl)thiazole

HRID 523160Notes

Reaction equation

HRID 523160 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([C:9]2[S:10][CH:11]=[CH:12][N:13]=2)[CH:3]=1.B(O)(O)[C:15]1[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1COCC1>CCOC(C)=O.[Cl-].[Na+].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].O>[Cl:1][C:2]1[CH:7]=[C:6]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)[N:5]=[C:4]([C:9]2[S:10][CH:11]=[CH:12][N:13]=2)[CH:3]=1

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 79799Tolylboronic acidHCID 901181032-(4,6-Dichloropyridin-2-yl)thiazole

Product 1

HCID 901178882-(4-Chloro-6-(p-tolyl)pyridin-2-yl)thiazoleYield 45%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a 2 dram vial equipped with a stir bar was added 2-(4,6-dichloropyridin-2-yl)thiazole (50 mg, 0.22 mmol), p-tolylboronic acid (29 mg, 0.22 mmol), Pd(dppf)Cl2 (8 mg, 11 μmol) and K3PO4 (344 mg, 1.62 mmol). The vial was capped with a septum screw-cap and then placed under N2 atmosphere. To the vial was added THF (1 mL) and water (0.5 mL). The mixture was placed in a 60° C. oil bath with stirring for 16 h. The reaction mixture was diluted with EtOAc (5 mL) and brine (1 mL). The mixture was shaken; the aq. phase was decanted away via pipet. The organic phase was dried over MgSO4; filtered; and the filtrate was concentrated in vacuo to afford a dark amber solid. This material was subjected to silica gel chromatography (hexanes:EtOAc, 100:0 to 60:40) to afford 2-(4-chloro-6-(p-tolyl)pyridin-2-yl)thiazole as a white solid (28 mg, 45%). 1H-NMR (400 MHz, CDCl3) δ 8.12 (d, J=1.8 Hz, 1H), 8.00 (d, J=8.3 Hz, 2H), 7.96 (d, J=3.3 Hz, 1H), 7.74 (d, J=1.8 Hz, 1H), 7.50 (d, J=3.3 Hz, 1H), 7.33 (d, J=8.0 Hz, 2H), 2.44 (s, 3H).

Workup

  1. customTo a 2 dram vial equipped with a stir bar
  2. customThe vial was capped with a septum
  3. customscrew-cap
  4. customwas placed in a 60° C.
  5. stirringThe mixture was shaken
  6. customthe aq. phase was decanted away via pipet
  7. dry with materialThe organic phase was dried over MgSO4
  8. filtrationfiltered
  9. concentrationand the filtrate was concentrated in vacuo
  10. customto afford a dark amber solid

Sources & evidence

ORD record
ord-b55d5167343b49cc9f65895f36c58ee3
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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