Ethyl Acetate → HCID 59580731, compound

HRID 533308Notes

Reaction equation

HRID 533308 reaction equation
FC(F)(F)[C:3]([N:5]([C:7]1[S:11][C:10]([C:12]2[CH:13]=[N:14][CH:15]=[C:16]([F:18])[CH:17]=2)=[N:9][CH:8]=1)C)=O.[OH-:21].[Na+].[C:23](OCC)(=O)C.[CH3:29][C:30]([CH3:36])([CH2:34]C)[C:31](Cl)=[S:32]>CO.CN(C)C1C=CN=CC=1.ClCCCl>[F:18][C:16]1[CH:17]=[C:12]([C:10]2[S:11][C:7]([N:5]([CH3:3])[C:34](=[O:21])[C:30]([CH3:36])([CH3:29])[CH2:31][S:32][CH3:23])=[CH:8][N:9]=2)[CH:13]=[N:14][CH:15]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 21397846HCID 21397846, compoundHCID 59580975HCID 59580975, compound

Product 1

HCID 59580731HCID 59580731, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolvent2×HCID 887MethanolSolvent

Procedure

To a solution of 2,2,2-trifluoro-N-[2-(5-fluoro-pyridin-3-yl)-thiazol-5-yl]-N-methyl-acetamide (244 mg, 0.80 mmol) in methanol (6 mL) was added an aqueous solution of sodium hydroxide (160 mg, 4 mmol, in 3 mL H2O), and the mixture was stirred at room temperature for 45 min. To this solution was added pH 7.0 aqueous buffer and ethyl acetate. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. To this crude material was added DCE (5 mL), 4-dimethylaminopyridine (DMAP, 300 mg, 2.5 mmol) and then a solution of the 2,2-dimethyl-3-methylthiopropionyl chloride (250 mg, 1.5 mmol) in DCE (3.0 mL). This mixture was heated to 75° C. and stirred overnight. The heterogeneous mixture thus obtained was loaded directly onto a chromatographic column Silica gel chromatography (0 to 100% ethyl acetate/hexanes) afforded the product as a red solid (161 mg, 59%): mp 98-102° C.; 1H NMR (300 MHz, CDCl3) δ 8.95 (app s, 1H), 8.51 (d, J=2.8 Hz, 1H), 7.98 (app dt, J=9.3, 2.5 Hz, 1H), 7.66 (s, 1H), 3.59 (s, 3H), 2.87 (s, 3H), 2.17 (s, 2H), 1.47 (s, 6H); ESIMS m/z 340 (M+1).

Workup

  1. additionTo this solution was added pH 7.0 aqueous buffer
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. temperatureThis mixture was heated to 75° C.
  8. stirringstirred overnight
  9. customThe heterogeneous mixture thus obtained

Sources & evidence

ORD record
ord-69353940fa6f40fda7b78a16b13553c9
Source dataset
uspto-grants-2014_10
Patent number
US08853246B2

Reaction notes

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