Tetrahydrofuran → HCID 90117944, compound

HRID 523161Notes

Reaction equation

HRID 523161 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.[CH:14]([O:17][C:18]1[CH:23]=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][N:19]=1)([CH3:16])[CH3:15].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1COCC1>CCOC(C)=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:3]=[C:4]([C:9]2[S:10][CH:11]=[CH:12][N:13]=2)[N:5]=[C:6]([C:21]2[CH:20]=[N:19][C:18]([O:17][CH:14]([CH3:16])[CH3:15])=[CH:23][CH:22]=2)[CH:7]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 242087982-[(Propan-2-yl)oxy]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 901181032-(4,6-Dichloropyridin-2-yl)thiazole

Product 1

HCID 90117944HCID 90117944, compoundYield 47%

Reagents, catalysts & solvents 3

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

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), 2-isopropoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (85 mg, 0.33 mmol), Pd(dppf)Cl2 (8.0 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 (0.50 mL). The mixture was placed in a 60° C. oil bath with stirring for 6 h. The reaction mixture was diluted with EtOAc (4 mL) and the aqueous phase was decanted away. The organic phase was diluted with EtOAc to a volume of 40 mL. The solution was dried over MgSO4; filtered; then concentrated in vacuo to afford a dark residue. This material was subjected to silica gel chromatography (hexanes:EtOAc, 100:0 to 85:15) to afford 2-(4-chloro-6′-isopropoxy-[2,3′-bipyridin]-6-yl)thiazole as a white solid (34 mg, 47%). 1H-NMR (400 MHz, CDCl3) δ 8.92-8.87 (m, 1H), 8.32-8.25 (m, 1H), 8.13 (d, J=1.8 Hz, 1H), 7.96 (d, J=3.0 Hz, 1H), 7.68 (d, J=1.8 Hz, 1H), 7.50 (d, J=3.0 Hz, 1H), 6.82 (dd, J=8.8, 0.5 Hz, 1H), 5.41 (spt, J=6.2 Hz, 1H), 1.41 (d, J=6.3 Hz, 6H).

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. customthe aqueous phase was decanted away
  6. additionThe organic phase was diluted with EtOAc to a volume of 40 mL
  7. dry with materialThe solution was dried over MgSO4
  8. filtrationfiltered
  9. concentrationthen concentrated in vacuo
  10. customto afford a dark residue

Sources & evidence

ORD record
ord-e8b13a40aca74645ae4e4c7f3fa1958d
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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