Potassium Phosphate, Tribasic → HCID 86663669, compound

HRID 879073Notes

Reaction equation

HRID 879073 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11](OS(C(F)(F)F)(=O)=O)=[C:10]([CH:22]=[O:23])[CH:9]=2)=[C:4]([F:24])[CH:3]=1.[CH:25]1(B(O)O)[CH2:27][CH2:26]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Br-].[Na+]>O.C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:25]3[CH2:27][CH2:26]3)=[C:10]([CH:22]=[O:23])[CH:9]=2)=[C:4]([F:24])[CH:3]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 253881Sodium BromideHCID 2760897Cyclopropylboronic acidHCID 86663668HCID 86663668, compound

Product 1

HCID 86663669HCID 86663669, compoundYield 36%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of trifluoromethanesulfonic acid 4′-chloro-2′-fluoro-3-formylbiphenyl-4-yl ester (30.0 g, 0.078 mol), cyclopropyl boronic acid (8.80 g, 0.10 mol), potassium phosphate (58.40 g, 0.28 mol) and sodium bromide (8.0 g, 0.078 mol) is added toluene (300 ml) then distilled water (30 ml) under a nitrogen atmosphere. To this mixture is then added tetrakis(triphenylphosphine) palladium (9.60 g, 8.40 mmol) in one portion, and the mixture is then heated at 100° C. overnight. After cooling to room temperature the mixture is diluted with distilled water (500 ml) and ethyl acetate (500 ml), and the two layers are separated and the aqueous phase extracted again with ethyl acetate (2×500 ml). Organic fractions are combined, washed with distilled water (1 L) then brine (1 L), and then dried over magnesium sulphate. The suspension is filtered and the filtrate concentrated in vacuo. The crude product is purified by flash column chromatography on silica gel, then additionally by flash column chromatography on basic alumina (10% ethyl acetate in hexane as eluant) to afford 4′-chloro-4-cyclopropyl-2′-fluoro-biphenyl-3-carbaldehyde (7.6 g, 36%).

Workup

  1. customthe two layers are separated
  2. extractionthe aqueous phase extracted again with ethyl acetate (2×500 ml)
  3. washwashed with distilled water (1 L)
  4. dry with materialbrine (1 L), and then dried over magnesium sulphate
  5. filtrationThe suspension is filtered
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe crude product is purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-39362a226b0942b6908460f6f56def7d
Source dataset
uspto-grants-2015_03
Patent number
US08987476B2

Reaction notes

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