3-Hydroxybenzaldehyde → 3-(2,2,2-Trifluoroethoxy)benzaldehyde

HRID 48073

Reaction equation

HRID 48073 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].CO.C[O-].[Na+].[F:15][C:16]([F:30])([F:29])[CH2:17]OS(C1C=CC(C)=CC=1)(=O)=O>CCCCCC.C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:15][C:16]([F:30])([F:29])[CH2:17][O:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6]

Participants

8

Reactant 4

HCID 1013-HydroxybenzaldehydeHCID 887Methanol2×HCID 67942Ethanol, 2,2,2-trifluoro-, 1-(4-methylbenzenesulfonate)HCID 10942334Sodium Methoxide

Product 1

HCID 47709473-(2,2,2-Trifluoroethoxy)benzaldehydeYield 26%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Ex-659A) 3-Hydroxybenzaldehyde (12.22 g, 0.10 mol) and 100 mL of anhydrous methanol were combined in a 250 mL round-bottom flask. Sodium methoxide was slowly added as a 25 wt. % solution in methanol (21.61 g, 0.10 mol), and the methanol was removed under vacuum. Then 2,2,2-trifluoroethyl-p-toluenesulfonate (25.42 g, 0.10 mol) was added, the flask was purged with nitrogen, and 100 mL of N-methyl pyrrolidine was added. The solution was stirred for 24 h at 90° C., quenched with water, and extracted with ether (3×). The combined ether layers were washed with 1 M NaOH (2×), water, and brine, dried over MgSO4, filtered, and evaporated to give 11.72 g of crude product. Chromatography over silica gel eluting with 0-10% ethyl acetate in hexane followed by a second chromatography with toluene gave 5.24 g (26%) of the desired 3-(2,2,2-trifluoroethoxy)benzaldehyde product as a pale oil. 1H NMR (C6D6) δ9.61 (s, 1H), 7.14 (d, 1H), 7.06 (s, 1H), 6.97 (t, 1H), 6.75 (m, 1H), 3.75 (m, 2H). 19F NMR (C6D6) δ−74.45 (t, 3F).

Workup

  1. customthe methanol was removed under vacuum
  2. customthe flask was purged with nitrogen, and 100 mL of N-methyl pyrrolidine
  3. additionwas added
  4. customquenched with water
  5. extractionextracted with ether (3×)
  6. washThe combined ether layers were washed with 1 M NaOH (2×), water, and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto give 11.72 g of crude product

Sources & evidence

ORD record
ord-72a3914148454fbd847d2af401c23c23
Source dataset
uspto-grants-2004_03
Patent number
US06699898B2

Linked notes

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