Ethyl Acetate → HCID 90403164, compound

HRID 1049370Notes

Reaction equation

HRID 1049370 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[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:23]1[S:27][CH:26]=[N:25][CH:24]=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>[N+:15]([C:12]1[N:11]=[CH:10][C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:23]3[S:27][CH:26]=[N:25][CH:24]=3)[CH:7]=2)=[CH:14][CH:13]=1)([O-:17])=[O:16]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 522689Potassium FluorideHCID 27632575-(Tributylstannyl)-1,3-thiazoleHCID 593227792-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridine

Product 1

HCID 90403164HCID 90403164, compoundYield 50.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of Example A1 (0.3 g, 1.192 mmol) in toluene (10 mL) was sparged with Ar, treated with 5-(tributylstannyl)thiazole (0.446 g, 1.192 mmol), Pd(PPh3)4 (0.138 g, 0.119 mmol) and heated at 110° C. for 16 h. The mixture was cooled to RT, treated with EtOAc and 10% aq. KF solution (30 mL) and stirred for 1 h. The solids were removed via filtration through diatomaceous earth, and the layers of the filtrate were separated. The aqueous layer was 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 (EtOAc/Hex) to afford 5-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)thiazole (180 mg, 50%) as a pale orange solid. 1H NMR (400 MHz, DMSO-d6): δ 9.16 (s, 1H), 8.64-8.63 (m, 2H), 8.57 (d, J=5.7 Hz, 1H), 8.43 (d, J=8.9 Hz, 1H), 8.04 (dd, J=8.9, 2.8 Hz, 1H), 7.89 (d, J=2.4 Hz, 1H), 7.15 (dd, J=5.7, 2.4 Hz, 1H); MS (ESI) m/z: 301.1 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. customThe solids were removed via filtration through diatomaceous earth
  3. customthe layers of the filtrate were separated
  4. extractionThe aqueous layer was 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 (EtOAc/Hex)

Sources & evidence

ORD record
ord-6356a6276835462d8289447dc4b6457b
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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