3,4,5-Trifluorobenzaldehyde → 3,5-Difluoro-4-(methylthio)benzaldehyde

HRID 1468830Notes

Reaction equation

HRID 1468830 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1F)[CH:5]=[O:6].[CH3:12][S-:13].[Na+]>CS(C)=O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1[S:13][CH3:12])[CH:5]=[O:6]

Participants

5

Reactant 2

HCID 27769543,4,5-TrifluorobenzaldehydeHCID 4378561Sodium methanethiolate

Product 1

HCID 227466823,5-Difluoro-4-(methylthio)benzaldehyde

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
125 °C

Procedure

A solution of 3,4,5-trifluorobenzaldehyde (1.0 g, 6.3 mmol) in DMSO (7.8 mL) was treated with a slurry of sodium methanethiolate (0.438 g, 6.25 mmol) in DMSO (0.3 mL). The solution was warmed at 125° C. for 17 min in a microwave. Upon completion, the reaction was diluted with EtOAc and washed with H2O (1×) and saturated aqueous NaCl (1×). The combined aqueous was back-extracted with EtOAc (3×), and the combined organic layer was dried over Na2SO4, filtered and evaporated in vacuo to yield a crude oil that was purified by silica gel column chromatography (0-30%, EtOAc-hexanes) to yield the title compound. 1H NMR (500 MHz, CDCl3) δ 9.88 (s, 1H), 7.39 (d, J 7.0 Hz, 2H), 2.58 (s, 3H).

Workup

  1. washwashed with H2O (1×) and saturated aqueous NaCl (1×)
  2. extractionThe combined aqueous was back-extracted with EtOAc (3×)
  3. dry with materialthe combined organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto yield a crude oil that
  7. customwas purified by silica gel column chromatography (0-30%, EtOAc-hexanes)

Sources & evidence

ORD record
ord-ff7f1f6b986a473cb2ea8000daceae1d
Source dataset
uspto-grants-2015_04
Patent number
US09006228B2

Reaction notes

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