Dichloromethane → HCID 53744375, compound

HRID 1743419Notes

Reaction equation

HRID 1743419 reaction equation
[C:1]([O-:4])([O-])=O.[K+].[K+].[CH2:7]([O:9][C:10](=[O:23])[C:11]1[CH:16]=[C:15](I)[C:14]([O:18][CH2:19][CH2:20][OH:21])=[C:13](Br)[CH:12]=1)[CH3:8].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(Cl)Cl.B(O)O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[CH2:7]([O:9][C:10](=[O:23])[C:11]1[CH:16]=[C:15]([C:29]2[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=2)[C:14]([O:18][CH2:19][CH2:20][OH:21])=[C:13]([C:11]2[CH:16]=[CH:15][C:14]([O:4][CH3:1])=[CH:13][CH:12]=2)[CH:12]=1)[CH3:8]

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 61668Boronic AcidHCID 201262(4-Methoxyphenyl)boronic acidHCID 113389853-Bromo-4-(2-hydroxyethoxy)-5-iodobenzoic acid ethyl ester

Product 1

HCID 53744375HCID 53744375, compoundYield 47.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 2N K2CO3 (108 mL) was added dioxane (875 mL), 3-bromo-4-(2-hydroxyethoxy)-5-iodobenzoic acid ethyl ester (25.34 g, 61.05 mmol), 4-methoxyphenyl boronic acid (12.43 g, 79.37 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with CH2Cl2 (1.49 g, 1.83 mmol). After stirring at room temperature for 1 h, the mixture was heated at 60° C. for 2.5 h. Progress was monitored by TLC. Additional quantities of catalyst and boronic acid (0.5 g) were added to push the reaction to completion. The reaction was cooled and partitioned between ethyl acetate/0.5 N HCl. The organic phase was washed with 0.5 N HCl, then brine. It was dried (MgSO4), decolorized (charcoal), and concentrated to give a residue which was filtered through a pad of SiO2. Purification by HPLC (ethyl acetate/hexane) afforded 11.47 g (47.5%) of mono-arylated product as a white solid [1H NMR (DMSO-d6) δ 8.08 (d, 1H), 7.82 (d, 1H), 7.50 (d, 2H), 7.02 (d, 2H), 4.65 (t, 1H), 4.30 (q, 2H), 3.81 (s, 3H), 3.59–3.42 (m, 4H), 1.29 (t, 3H)] and 6.61 g (25.6%), of bis-arylated product as a brown oil: 1H NMR (DMSO-d6) δ 7.82 (s, 2H), 7.52 (d, 4H), 7.00 (d, 4H), 4.30 (q, 2H), 3.80 (s, 6H), 3.25 (m, 2H), 3.12 (m, 2H), 1.31 (t, 3H).

Workup

  1. temperaturethe mixture was heated at 60° C. for 2.5 h
  2. customthe reaction to completion
  3. temperatureThe reaction was cooled
  4. custompartitioned between ethyl acetate/0.5 N HCl
  5. washThe organic phase was washed with 0.5 N HCl
  6. dry with materialIt was dried (MgSO4)
  7. concentrationconcentrated
  8. customto give a residue which
  9. filtrationwas filtered through a pad of SiO2
  10. customPurification by HPLC (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-6ff0fca2f75544b0a44f00afa47389ce
Source dataset
uspto-grants-2006_03
Patent number
US07008636B2

Reaction notes

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