Trifluoroacetic acid → HCID 46317762, compound

HRID 2402104Notes

Reaction equation

HRID 2402104 reaction equation
OC(C1C=CC2C(=CC=CC=2)C=1)[C:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[S:5][C:4]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15].FC(F)(F)C(O)=O.C([SiH](CC)CC)C>C(Cl)Cl>[N:11]1[CH:10]=[CH:9][C:8]([C:6]2[S:5][C:4]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:3][CH:7]=2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 12052Triethylsilane2×HCID 66748221HCID 66748221, compound

Product 1

HCID 46317762HCID 46317762, compoundYield 121.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Ethyl 3-[hydroxy(2-naphthyl)methyl]-5-pyridin-4-ylthiophene-2-carboxylate (118.0 mg, 0.3030 mmol), methylene chloride (2.4 mL), trifluoroacetic acid (140.0 uL, 1.818 mmol), and triethylsilane (84.7 uL, 0.530 mmol) were combined in a round bottomed flask equipped with a stirbar. The reaction was stirred overnight at room temperature under an atmosphere of nitrogen. An aliquot was taken from the reaction, quenched into water, basified with sodium carbonate, and extracted with ethyl acetate. TLC analysis (2:1 ethyl acetate:DCM) indicated that the starting ester was ˜50% converted to a slightly higher Rf product. Additional trifluoroacetic acid (300 uL, 4 mmol) and triethylsilane (200 uL, 1 mmol) were added and the reaction was stirred at room temperature under an atmosphere of nitrogen for another 4 hours. LCMS analysis showed one major peak with correct ES+ for product with a small amount of SM remaining. The reaction was quenched into water, basified, and extracted into ethyl acetate. The extract was washed with saline, dried over sodium sulfate, filtered, and evaporated to leave crude product as an oil. The crude product was dissolved in minimal DCM then was purified by column chromatography on silica gel (gradient 100% DCM to 50% ethyl acetate) to afford product 86 mg (76% yield) as a white solid. LC/MS (FA) ES+ 374. 1H NMR (400 MHz, DMSO) δ 8.64-8.55 (m, 2H), 7.90-7.80 (m, 4H), 7.80-7.75 (s, 1H), 7.73-7.66 (m, 2H), 7.52-7.40 (m, 3H), 4.57-4.49 (s, 2H), 4.39-4.27 (q, J=7.1 Hz, 2H), 1.35-1.25 (t, J=7.1 Hz, 3H).

Workup

  1. customequipped with a stirbar
  2. customAn aliquot was taken from the reaction
  3. customquenched into water
  4. extractionextracted with ethyl acetate
  5. stirringthe reaction was stirred at room temperature under an atmosphere of nitrogen for another 4 hours
  6. customThe reaction was quenched into water
  7. extractionextracted into ethyl acetate
  8. washThe extract was washed with saline
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customto leave crude product as an oil
  13. customthen was purified by column chromatography on silica gel (gradient 100% DCM to 50% ethyl acetate)

Sources & evidence

ORD record
ord-55639d46458745b386a458b794fd9249
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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