Ethyl Acetate → HCID 90404051, compound

HRID 1049373Notes

Reaction equation

HRID 1049373 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:18])=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C([Sn](CCCC)(CCCC)[C:24]1[S:28][CH:27]=[N:26][CH:25]=1)CCC.CCOC(C)=O.[F-].[K+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:18][C:10]1[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:24]3[S:28][CH:27]=[N:26][CH:25]=3)[CH:7]=2)=[CH:14][CH:13]=[C:12]([N+:15]([O-:17])=[O:16])[N:11]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 522689Potassium FluorideHCID 27632575-(Tributylstannyl)-1,3-thiazoleHCID 904036213-((2-Chloropyridin-4-yl)oxy)-2-methyl-6-nitropyridine

Product 1

HCID 90404051HCID 90404051, compoundYield 65.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of Example A4 (0.35 g, 1.318 mmol) in toluene (8 mL) was sparged with Ar, treated with 5-(tributylstannyl)thiazole (0.493 g, 1.318 mmol) and Pd(PPh3)4 (0.152 g, 0.132 mmol), heated at 110° C. for 16 h, then cooled to RT. The mixture was treated with EtOAc and 10% aq. KF solution, stirred for 1 h and the solids were removed via filtration through diatomaceous earth. The layers of the filtrate were separated, the aqueous layer extracted with additional EtOAc (1×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 5-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)thiazole (270 mg, 65%) as a pale orange solid. 1H NMR (400 MHz, DMSO-d6): δ 9.14 (s, 1H), 8.62 (s, 1H), 8.53 (d, J=5.7 Hz, 1H), 8.24 (d, J=8.7 Hz, 1H), 7.90 (d, J=8.7 Hz, 1H), 7.81 (d, J=2.4 Hz, 1H), 7.06 (dd, J=5.7, 2.4 Hz, 1H), 2.51 (s, 3H); MS (ESI) m/z: 315.1 (M+H+).

Workup

  1. temperaturecooled to RT
  2. customthe solids were removed via filtration through diatomaceous earth
  3. customThe layers of the filtrate were separated
  4. extractionthe aqueous layer extracted with additional EtOAc (1×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-c5b14a20eebe43a2a7d0d58f2267a119
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

Loading…