Toluene → HCID 57196815, compound

HRID 2187521Notes

Reaction equation

HRID 2187521 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([OH:18])=[O:17])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].CN(C)C=O.[C:24](Cl)(=O)C(Cl)=O.[Cl-].[NH4+].[C:32]1([CH3:38])[CH:37]=CC=C[CH:33]=1>>[Br:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([O:18][CH2:33][C:32]([CH3:38])([CH3:24])[CH3:37])=[O:17])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

6

Reactant 5

HCID 1140TolueneHCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 18476095HCID 18476095, compound

Product 1

HCID 57196815HCID 57196815, compound

Conditions

Temperature
50 °C

Procedure

A stirred mixture of 3′-bromo-4′-methoxy-[1,1′-biphenyl]4-carboxylic acid (19.2 g, 62.5 mmol) and dimethylformamide (0.1 mL) in toluene (200 mL) at 20° C. is treated with oxalyl chloride (11.0 mL, 126 mmol). The mixture is then heated at 50° C. for 1 h and then evaporated to dryness under reduced pressure. The resulting crude acid chloride is dissolved in dry tetrahydrofuran (250 mL) and added dropwise to a stirred solution of lithium tert-butylate in tetrahydrofuran (prepared by the slow addition of 32.5 mL of n-butyl lithium to a solution of 23.5 mL of dry t-butanol in 200 mL of dry tetrahydrofuran at 20° C). The mixture is stirred for an additional 2 h, then treated with a saturated aqueous solution of ammonium chloride (400 mL) and extracted with t-butylethyl ether (2×300 mL). The combined extracts are dried (Na2SO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by chromatography (silica gel, 20% ethyl acetate in cyclohexane) and recrystallised from t-butylethyl ether-hexane to give 3′-bromo-4′-methoxy-[1,1′-biphenyl]-4-carboxylic acid, 2,2-dimethylpropyl ester as a colourless crystalline solid.

Workup

  1. customevaporated to dryness under reduced pressure
  2. dissolutionThe resulting crude acid chloride is dissolved in dry tetrahydrofuran (250 mL)
  3. additionadded dropwise to a stirred solution of lithium tert-butylate in tetrahydrofuran (
  4. customprepared by the slow addition of 32.5 mL of n-butyl lithium to a solution of 23.5 mL of dry t-butanol in 200 mL of dry tetrahydrofuran at 20° C)
  5. extractionextracted with t-butylethyl ether (2×300 mL)
  6. dry with materialThe combined extracts are dried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent is evaporated off under reduced pressure
  9. customto yield the crude product which
  10. customis purified by chromatography (silica gel, 20% ethyl acetate in cyclohexane)
  11. customrecrystallised from t-butylethyl ether-hexane

Sources & evidence

ORD record
ord-25102a6e1e0347e781e056cfcffdec34
Source dataset
uspto-grants-2002_06
Patent number
US06410547B1

Reaction notes

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