Proton sponge → 3-Chloro-5-methoxybenzaldehyde

HRID 370305Notes

Reaction equation

HRID 370305 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:18][CH3:19])[C:9]=1OS(C(F)(F)F)(=O)=O)[CH:5]=[O:6].CN(C1C2C(N(C)C)=CC=CC=2C=CC=1)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:18][CH3:19])[CH:9]=1)[CH:5]=[O:6]

Participants

6

Reactant 2

HCID 88675Proton spongeHCID 183205273-Chloro-5-methoxy-4-trifluoromethanesulfonyloxy benzaldehyde

Product 1

HCID 219046333-Chloro-5-methoxybenzaldehydeYield 89%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

Triflate 5 (9 g, 28 mmol), palladium(II) acetate (120 mg, 0.5 mmol), 1,1'-bis(diphenylphosphino)ferrocene (620 mg, 1 mmol) and hplc grade CH3CN (10 ml) were mixed well in a teflon-lined stainless steel bomb. After adding freshly made, pulverized proton sponge formate2 (7.84 g, 30 mmol), the bomb was sealed and heated at 90° C. for 4 h. The cooled reaction was then filtered to remove proton sponge crystals, partitioned between EtOAc and 3N HCl, washed once each with dilute brine and dilute NaHCO3, dried over Na2SO4, and evaporated. Silica gel chromatography (15% EtOAc/hexanes) yielded 4.25 g (88.5%) of chloromethoxybenzaldehyde 6, mp 45° C.

Workup

  1. additionAfter adding freshly
  2. customthe bomb was sealed
  3. customThe cooled reaction
  4. filtrationwas then filtered
  5. customto remove proton sponge crystals
  6. custompartitioned between EtOAc and 3N HCl
  7. washwashed once each with dilute brine and dilute NaHCO3
  8. dry with materialdried over Na2SO4
  9. customevaporated

Sources & evidence

ORD record
ord-3275cc3f0e1c4d04a684dc259a7e9762
Source dataset
uspto-grants-2000_10
Patent number
US06140495

Reaction notes

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