Hydrochloric Acid → Dimethyl 5-(4-fluorophenoxy)isophthalate

HRID 1889644Notes

Reaction equation

HRID 1889644 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C(N(CC)CC)C.FOB(C1C=CC=CC=1)O.Cl>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.CO.CCOC(C)=O.C(Cl)(Cl)Cl>[F:16][C:17]1[CH:22]=[CH:21][C:20]([O:1][C:2]2[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=[C:4]([CH:3]=2)[C:12]([O:14][CH3:15])=[O:13])=[CH:19][CH:18]=1

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 830651,3-Benzenedicarboxylic acid, 5-hydroxy-, 1,3-dimethyl esterHCID 2856454-Fluorophenylboronic acidHCID 66616553HCID 66616553, compound2×

Product 1

HCID 66616627Dimethyl 5-(4-fluorophenoxy)isophthalateYield 85%

Reagents, catalysts & solvents 5

HCID 8895Cupric acetateCatalyst2×HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of dimethyl 5-hydroxyisophthalate (3.1 g, 14.75 mmol), 4-fluorophenylboronic acid (4.13 g, 29.5 mmol), copper(II) acetate (2.68 g, 14.75 mmol) and triethylamine (4.48 g, 44.2 mmol) in CH2Cl2 (65 mL) was stirred at rt in the open air for 38 h. An additional 1 g of fluorophenylboronic acid was added and the reaction mixture was continued to stir at rt in the open air. After 24 h, an additional 1 g of fluorophenylboronic acid and 300 mg of copper acetate were added to the reaction mixture and it was continued to stir for 6 h in the open air. The mixture was mixed with CHCl3 and aq HCl, the organic layer was separated, washed with aq HCl, aq NaHCO3, dried over MgSO4, concentrated, and the residue was purified by flash column chromatography on SiO2 eluting with Hexane:EtOAc:MeOH/800:200:40 to obtain the desired product (3.8 g, 12.49 mmol, 85% yield) as a white solid. 1H NMR (CDCl3): δ 8.36 (s, 1H), 7.75 (s, 2H), 7.06˜6.96 (m, 4H), 3.89 (s, 6H).

Workup

  1. stirringto stir at rt in the open air
  2. waitAfter 24 h
  3. stirringto stir for 6 h in the open air
  4. customthe organic layer was separated
  5. washwashed with aq HCl, aq NaHCO3
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customthe residue was purified by flash column chromatography on SiO2 eluting with Hexane

Sources & evidence

ORD record
ord-245c996330624509804f3899d4307b31
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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