Hydrochloric Acid → HCID 90414660, compound

HRID 57401Notes

Reaction equation

HRID 57401 reaction equation
Cl[C:2]1[S:3][C:4]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([C:14]([CH3:20])([CH3:19])[C:15]([F:18])([F:17])[F:16])[CH:9]=2)=[C:5]([CH3:7])[N:6]=1.C([Sn](CCCC)(CCCC)[C:26]([O:28]CC)=[CH2:27])CCC.[F-].[K+].Cl.[OH-].[Na+]>O1CCOCC1.CCOC(C)=O.C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:7][C:5]1[N:6]=[C:2]([C:26](=[O:28])[CH3:27])[S:3][C:4]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C:14]([CH3:20])([CH3:19])[C:15]([F:18])([F:17])[F:16])[CH:9]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 522689Potassium FluorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 90416122HCID 90416122, compound

Product 1

HCID 90414660HCID 90414660, compoundYield 49%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-chloro-4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazole (3.3 g, 10.3 mmol) and Pd(PPh3)2Cl2 (0.72 g, 1.03 mmol) in 50 mL dioxane under nitrogen, tributyl(1-ethoxyvinyl)stannane (3.82 ml, 11.32 mmol) was added. The mixture was heated to 100 C for 16 h. The reaction was cooled to r.t. and diluted with 25 mL EtOAc. 2M KF (15.4 ml) solution was added and stirred for 1 h. Copious precipitate formed. The reaction was filtered through Celite and chased with EtOAc. The organic layer was rinsed with 60 mL water, and concentrated to give grey solid. Crude solid was dissolved in THF (50 mL) and 1N HCl (20.58 mL) was added. The reaction was stirred at r.t. for 2 h. The mixture was neutralized by addition of 1 N NaOH. THF was removed in vacuo. Extracted aqueous with 2×50 mL EtOAc. The organic layers were washed with 50 mL brine, and dried over Na2SO4. Filtered and concentrated on silica gel. Flash chromatography using 10-50% EtOAc in heptane gave 1.65 g (49%) 1-(4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)ethanone as a yellow oil. MS m/z 329.0 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.72 (dd, J=5.2, 0.9 Hz, 1H), 7.60 (dq, J=1.8, 0.9 Hz, 1H), 7.34 (dd, J=5.1, 1.6 Hz, 1H), 2.74 (s, 3H), 2.63 (s, 3H), 1.69 (s, 6H).

Workup

  1. temperatureThe mixture was heated to 100 C for 16 h
  2. customCopious precipitate formed
  3. filtrationThe reaction was filtered through Celite
  4. washThe organic layer was rinsed with 60 mL water
  5. concentrationconcentrated
  6. customto give grey solid
  7. stirringThe reaction was stirred at r.t. for 2 h
  8. customTHF was removed in vacuo
  9. washThe organic layers were washed with 50 mL brine
  10. dry with materialdried over Na2SO4
  11. filtrationFiltered
  12. concentrationconcentrated on silica gel

Sources & evidence

ORD record
ord-00aa21b0c08343479ca182f5e3031ada
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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