Phenylboronic Acid → Oxalate

HRID 572825Notes

Reaction equation

HRID 572825 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:8]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[C:9]2[S:10][C:11]3[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=3[N:13]=2)[CH:5]=[CH:6][CH:7]=1.[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[C:35]([O-:40])(=[O:39])[C:36]([O-:38])=[O:37]>CC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[Fe+2]>[C:2]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[C:9]2[S:10][C:11]3[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=3[N:13]=2)[CH:3]=1.[C:35]([O-:40])(=[O:39])[C:36]([O-:38])=[O:37]

Participants

8

Reactant 3

HCID 66827Phenylboronic AcidHCID 71081OxalateHCID 569474582-[(3-Iodophenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole

Product 2

HCID 71081OxalateHCID 668359972-[Biphenyl-3-yl(1-methylpiperidin-4-yloxy)methyl]benzothiazole

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 152416121,1`-Bis(diphenylphosphino)ferroceneCatalystHCID 180AcetoneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 2-[(3-iodophenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole (200 mg), phenylboronic acid (70 mg), palladium acetate (4.8 mg) and 1,1-bis(diphenylphosphino)ferrocene is placed in a round-bottom flask and purged with argon. A 1M aqueous degassed solution of potassium carbonate (1.51 mL) and degassed tetrahydrofuran (2 mL) are introduced. The mixture is heated at 95° C. for 30 min, cooled back to room temperature and filtered over a celite pad. The cake is rinsed with ethyl acetate and water. The pooled phases are decanted. The organic phase is dried over magnesium sulfate and concentrated. The residue is purified by column chromatography (gradient dichloromethane/methanol from 98/2 to 90/10) to give the crude base which is then converted to the oxalate in acetone to give 2-[biphenyl-3-yl(1-methylpiperidin-4-yloxy)methyl]benzothiazole, oxalate as a beige amorphous solid.

Workup

  1. customis placed in a round-bottom flask
  2. custompurged with argon
  3. customA 1M aqueous degassed solution of potassium carbonate (1.51 mL) and degassed tetrahydrofuran (2 mL)
  4. additionare introduced
  5. temperaturecooled back to room temperature
  6. filtrationfiltered over a celite pad
  7. washThe cake is rinsed with ethyl acetate and water
  8. customThe pooled phases are decanted
  9. dry with materialThe organic phase is dried over magnesium sulfate
  10. concentrationconcentrated
  11. customThe residue is purified by column chromatography (gradient dichloromethane/methanol from 98/2 to 90/10)
  12. customto give the crude base which

Sources & evidence

ORD record
ord-e5341bf0124d43ddaaa765fcaf8ac944
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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