Potassium Carbonate → 4'-Chlorobiphenyl-2-carbaldehyde

HRID 2406225Notes

Reaction equation

HRID 2406225 reaction equation
Br[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[Cl:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C(O)C.COCCOC.C(=O)([O-])[O-].[K+].[K+]>O>[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C:2]2[C:3]([CH:4]=[O:5])=[CH:6][CH:7]=[CH:8][CH:9]=2)=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 811292-BromobenzaldehydeHCID 20074477Dimethoxyethane ethanol

Product 1

HCID 13936894'-Chlorobiphenyl-2-carbaldehydeYield 71%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 2-bromobenzaldehyde (18.0 g, 97.0 mmol) and 4-chloro-phenylboronic acid (19.0 g, 122 mmol) in a 1:1 mixture of ethanol/DME (400 mL) is added a solution of potassium carbonate (26.9 g, 195 mmol) in water (100 mL), and the reaction mixture is purged with nitrogen for 30 minutes. Tetrakis(triphenyl-phosphine)palladium (5.62 g, 4.86 mmol) is then added, and the reaction is purged again with nitrogen for 20 minutes. The pale yellow-green solution is heated to 75° C. and stirred for 20 hours. The reaction is then cooled to room temperature, diluted with ethyl acetate (200 mL), and filtered through a ZAPCAP filter. The filtrate is washed with brine (400 mL) and the aqueous layer is back-extracted with ethyl acetate (2×200 mL). The combined organic layers are dried over MgSO4 and concentrated to afford an orange oily solid. This crude material is purified via flash chromatography on silica gel (0-20% EtOAd heptanes) to afford the title compound (14.9 g, 71% yield). 1H NMR (400 MHz, CDCl3) δ 10.0 (s, 1H), 8.05 (d, J=7.5 Hz, 1H), 7.68 (t, J=6.2 Hz, 1H), 7.54 (t, J=7.4 Hz, 1H), 7.49 (d, J=9.4 Hz, 2H), 7.45 (d, J=9.1 Hz, 1H), 7.34 (d, J=8.5 Hz, 2H).

Workup

  1. customthe reaction mixture is purged with nitrogen for 30 minutes
  2. customthe reaction is purged again with nitrogen for 20 minutes
  3. temperatureThe reaction is then cooled to room temperature
  4. additiondiluted with ethyl acetate (200 mL)
  5. filtrationfiltered through a ZAPCAP
  6. filtrationfilter
  7. washThe filtrate is washed with brine (400 mL)
  8. extractionthe aqueous layer is back-extracted with ethyl acetate (2×200 mL)
  9. dry with materialThe combined organic layers are dried over MgSO4
  10. concentrationconcentrated
  11. customto afford an orange oily solid
  12. customThis crude material is purified via flash chromatography on silica gel (0-20% EtOAd heptanes)

Sources & evidence

ORD record
ord-31335524097440838668c03279b713bf
Source dataset
uspto-grants-2014_08
Patent number
US08809352B2

Reaction notes

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