Dimethylformamide → HCID 86663664, compound

HRID 879065Notes

Reaction equation

HRID 879065 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)=[CH:4][C:3]=1I.C([Mg]Br)(C)C.CN(C)[CH:23]=[O:24]>C(OCC)C.O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[CH:23]=[O:24]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 59445916HCID 59445916, compoundHCID 178418365HCID 178418365, compound

Product 1

HCID 86663664HCID 86663664, compoundYield 76.1%

Reagents, catalysts & solvents 1

HCID 21868444Ether tetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

To a solution of 4-bromo-4′-chloro-3-iodobiphenyl (4.80 g, 0.012 mol) (described in WO 2008/071405) in anhydrous diethyl ether/tetrahydrofuran (120 ml, 1:1 ratio) at −75° C. is added isopropyl magnesium bromide (18.96 ml, 15% solution in tetrahydrofuran) dropwise such as to maintain an internal temperature below −70° C. Once addition is complete the reaction mixture is stirred at −75° C. for 2 hours, then warmed to −45° C. Anhydrous N,N-dimethylformamide (1.71 g, 0.0184 mol) is next added dropwise, maintaining temperature below −40° C., followed by warming to room temperature and quenching with 2M hydrochloric acid (60 ml). The reaction mixture is further diluted with diethyl ether, the two phases separated, and the aqueous phase extracted with additional diethyl ether. The combined organic extracts are washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. The crude product is purified by flash column chromatography (2% ethyl acetate in hexane eluant) to afford 4-bromo-4′-chloro-biphenyl-3-carbaldehyde (2.7 g, 75%) as a white solid.

Workup

  1. temperatureto maintain an internal temperature below −70° C
  2. additionOnce addition
  3. temperaturewarmed to −45° C
  4. temperaturemaintaining temperature below −40° C.
  5. temperatureby warming to room temperature
  6. customquenching with 2M hydrochloric acid (60 ml)
  7. additionThe reaction mixture is further diluted with diethyl ether
  8. customthe two phases separated
  9. extractionthe aqueous phase extracted with additional diethyl ether
  10. washThe combined organic extracts are washed with brine
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationthe filtrate concentrated in vacuo
  14. customThe crude product is purified by flash column chromatography (2% ethyl acetate in hexane eluant)

Sources & evidence

ORD record
ord-8c944cb1cf544a86b1b2bafeb2b6bb89
Source dataset
uspto-grants-2015_03
Patent number
US08987476B2

Reaction notes

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