Methanesulfonic Acid → HCID 57524354, compound

HRID 623804Notes

Reaction equation

HRID 623804 reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[C:7]([C:15]2[N:19]=[CH:18][N:17](/[CH:20]=[CH:21]\[C:22]([NH:24][NH2:25])=[O:23])[N:16]=2)[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)([CH3:3])[CH3:2].[CH3:26]OC(OC)OC.CS(O)(=O)=O.CCOC(C)=O.CCCCCC>C1COCC1>[CH:1]([O:4][C:5]1[CH:6]=[C:7]([C:15]2[N:19]=[CH:18][N:17](/[CH:20]=[CH:21]\[C:22]3[O:23][CH:26]=[N:25][N:24]=3)[N:16]=2)[CH:8]=[C:9]([C:11]([F:13])([F:14])[F:12])[CH:10]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 9005Trimethyl orthoformateHCID 21226206Ethyl acetate hexaneHCID 70563237HCID 70563237, compound

Product 1

HCID 57524354HCID 57524354, compoundYield 13.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a 25-mL, 3N round-bottomed flask equipped with nitrogen inlet, and a rubber septum, (Z)-3-(3-(3-isopropoxy-5-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylohydrazide (0.29 g, 1.0 eq.) was dissolved in THF (7.5 mL, 26V), added trimethylorthoformate (0.095 g, 1.1 eq) and added methanesulphonic acid (0.048 g, 0.5 eq). The Reaction mixture was refluxed at 70° for 2-3 h. The progress of the reaction was followed by TLC analysis on silica gel with 50% EtOAc-hexane as mobile phase. SM Rf=0.40 and Product Rf=0.5. Reaction mixture was poured in to ice water (10 mL) and extracted with EtOAc (3×15 mL). The combined organic layers were washed with Brine solution. (3×15 mL), dried over MgSO4, filtered, and concentrated by rotary evaporation (25° C., 20 mmHg) to afford 0.28 g of crude compound. The crude reaction mixture was purified by column chromatography using silica 60/120 using ethyl acetate:hexane as mobile phase. The column (5×10 cm) was packed in hexane and started eluting in ethyl acetate in gradient manner starting with fraction collection (25-mL fractions) from 35% to 40% ethyl acetate in hexane. Compound started eluting with 35% ethylacetate in hexane. Fraction containing such TLC profile was collected together to obtain pure compound (40 mg), Yield (13.42%). 1H NMR (400 MHz, CDCl3) δ8.46-8.54 (d, 1H), 8 (t, 2H), 7.89 (s, 1H), 7.38-7.42 (d, 1H), 7.28 (d, 1H), 7.01-7.23 (d, 1H), 4.72-4.75 (d, J=11.6 Hz, 1H), 1.59 (d, 6H): LCMS for C16H14F3N5O2 [M+1]+ 365.31 found 365.89 at 3.986 min(LCMS 95.75%).

Workup

  1. customIn a 25-mL, 3N round-bottomed flask equipped with nitrogen inlet
  2. temperatureThe Reaction mixture was refluxed at 70° for 2-3 h
  3. customReaction mixture
  4. extractionextracted with EtOAc (3×15 mL)
  5. washThe combined organic layers were washed with Brine solution
  6. dry with material(3×15 mL), dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated by rotary evaporation (25° C., 20 mmHg)
  9. customto afford 0.28 g of crude compound
  10. customThe crude reaction mixture
  11. customwas purified by column chromatography
  12. washstarted eluting in ethyl acetate in gradient manner
  13. customstarting with fraction collection (25-mL fractions) from 35% to 40% ethyl acetate in hexane
  14. washCompound started eluting with 35% ethylacetate in hexane
  15. additionFraction containing such TLC profile
  16. customwas collected together

Sources & evidence

ORD record
ord-9a6af10365394693a4b2a0e367a27f83
Source dataset
uspto-grants-2016_04
Patent number
US09303000B2

Reaction notes

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