1,2-Dimethoxyethane → HCID 86663667, compound

HRID 879072Notes

Reaction equation

HRID 879072 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1B(O)O.[C:12](=[O:15])([O-])[O-].[Na+].[Na+].CO[CH2:20][CH2:21][O:22]C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]([C:2]2[CH:3]=[CH:4][C:21]([OH:22])=[C:20]([CH:12]=[O:15])[CH:7]=2)=[C:2]([F:1])[CH:7]=1

Participants

5

Reactant 3

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 4193595(4-Chloro-2-fluorophenyl)boronic acid

Product 1

HCID 86663667HCID 86663667, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

To a mixture of 5-bromosalicyaldehyde (30.0 g, 0.15 mol), 2-fluoro-4-chlorophenylboronic acid (30.0 g, 0.17 mol) and sodium carbonate (24.0 g, 0.23 mol) is added 1,2-dimethoxyethane (225 ml) and distilled water (75 ml), and the suspension is stirred under a nitrogen atmosphere. To this mixture is then added [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)chloride (4.5 g, 7.5 mmol), followed by heating at reflux overnight. After cooling to room temperature and dilution with distilled water (500 ml) and dichloromethane (500 ml), the two phases are separated, and the aqueous phase extracted again with dichloromethane (2×500 ml). Organic fractions are combined, washed with brine (800 ml) then dried over magnesium sulphate. The suspension is filtered and the filtrate is concentrated in vacuo. Then crude material is purified by flash column purification (5-10% ethyl acetate in isohexane eluant) to afford 4′-chloro-2′-fluoro-4-hydroxybiphenyl-3-carbaldehyde (33.61 g, 89%) as a pale yellow solid.

Workup

  1. distillationdistilled water (75 ml)
  2. temperatureby heating
  3. temperatureat reflux overnight
  4. customdilution with distilled water (500 ml) and dichloromethane (500 ml), the two phases are separated
  5. extractionthe aqueous phase extracted again with dichloromethane (2×500 ml)
  6. washwashed with brine (800 ml)
  7. dry with materialthen dried over magnesium sulphate
  8. filtrationThe suspension is filtered
  9. concentrationthe filtrate is concentrated in vacuo
  10. customThen crude material is purified by flash column purification (5-10% ethyl acetate in isohexane eluant)

Sources & evidence

ORD record
ord-dfac218861d74e4ea4a911c5cefb1064
Source dataset
uspto-grants-2015_03
Patent number
US08987476B2

Reaction notes

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