Oxalyl chloride → HCID 58528890, compound

HRID 1431025Notes

Reaction equation

HRID 1431025 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:12]=[C:11]([O:13][CH:14]([CH3:16])[CH3:15])[CH:10]=[C:6]([C:7]([OH:9])=O)[CH:5]=1.C(Cl)(C(Cl)=O)=O.[Br:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1>C(Cl)Cl.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.[Pd].S1C=CC=C1C([O-])=O.[Cu+].CN(C=O)C>[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:12]=[C:11]([O:13][CH:14]([CH3:16])[CH3:15])[CH:10]=[C:6]([C:7](=[O:9])[C:28]2[CH:29]=[CH:30][C:25]([Br:24])=[CH:26][CH:27]=2)[CH:5]=1

Participants

8

Reactant 3

HCID 65578Oxalyl chlorideHCID 79599(4-Bromophenyl)boronic acidHCID 58780911HCID 58780911, compound

Product 1

HCID 58528890HCID 58528890, compoundYield 86.4%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 1542701,5-Diphenylpenta-1,4-dien-3-one;palladiumCatalystHCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-isopropoxy-isophthalic acid monomethyl ester (1.90 g, 7.98 mmol) in DCM (50 mL) was added (COCl)2 (1.39 mL, 16.9 mmol) and DMF (0.03 mL, 0.400 mmol) at rt. After stirring at rt for 2 hr, the mixture was concentrated. The resulting residue was azeotroped with 50 mL anhydrous toluene and then re-dissolved in Et2O (40 mL). Palladium bis(dibenzylideneacetone) (229 mg, 0.400 mmol), copper (I) thiophene-2-carboxylate (1.52 g, 7.98 mmol), triphenylphosphohine (209 mg, 0.798 mmol), and 4-bromophenylboronic acid (3.20 g, 16.0 mmol) were added to the reaction flask. The resulting mixture was stirred at rt for 3 hr, filtered through a pad of Celite, rinsed with Et2O. The combined Et2O layers were concentrated. The residue was purified by silica gel flash chromatography (6×25 cm, hexane/EtOAc, v/v=5:1, 3:1). Fractions containing the coupling product were pooled and concentrated to give the title compound (2.60 g, 86%) as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.91 (m, 1H), 7.77 (m, 1H), 7.63-7.69 (m, 3H), 7.48 (m, 1H), 7.38-7.43 (m, 1H), 4.57 (m, 1H), 3.92 (s, 3H), 1.35 (d, J=6 Hz, 6H).

Workup

  1. concentrationthe mixture was concentrated
  2. customThe resulting residue was azeotroped with 50 mL anhydrous toluene
  3. dissolutionre-dissolved in Et2O (40 mL)
  4. stirringThe resulting mixture was stirred at rt for 3 hr
  5. filtrationfiltered through a pad of Celite
  6. washrinsed with Et2O
  7. concentrationThe combined Et2O layers were concentrated
  8. customThe residue was purified by silica gel flash chromatography (6×25 cm, hexane/EtOAc, v/v=5:1, 3:1)
  9. additionFractions containing the coupling product
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f755d49ceb6744019a35ed1df8af3686
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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