Methylboronic Acid → (R)-4-hydroxymethyl-3-{3-methanesulfonyl-4-[4-(4-methylbenzoyl)piperidine-1-carbonyl]phenyl}oxazolidin-2-one

HRID 1804176Notes

Reaction equation

HRID 1804176 reaction equation
Cl[C:2]1[CH:43]=[CH:42][C:5]([C:6]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([C:16]3[CH:21]=[CH:20][C:19]([N:22]4[C@H:26]([CH2:27][O:28]C(=O)C5C=CC=CC=5)[CH2:25][O:24][C:23]4=[O:37])=[CH:18][C:17]=3[S:38]([CH3:41])(=[O:40])=[O:39])=[O:15])[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[CH3:44]B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[F-].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.O1CCCC1>[OH:28][CH2:27][C@@H:26]1[CH2:25][O:24][C:23](=[O:37])[N:22]1[C:19]1[CH:20]=[CH:21][C:16]([C:14]([N:11]2[CH2:10][CH2:9][CH:8]([C:6](=[O:7])[C:5]3[CH:42]=[CH:43][C:2]([CH3:44])=[CH:3][CH:4]=3)[CH2:13][CH2:12]2)=[O:15])=[C:17]([S:38]([CH3:41])(=[O:39])=[O:40])[CH:18]=1

Participants

8

Reactant 4

HCID 139377Methylboronic AcidHCID 522689Potassium FluorideHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 54755002benzoic acid (R)-3-{4-[4-(4-chlorobenzoyl)piperidine-1-carbonyl]-3-methanesulfonylphenyl}-2-oxooxazolidin-4-ylmethyl ester

Product 1

HCID 67382025(R)-4-hydroxymethyl-3-{3-methanesulfonyl-4-[4-(4-methylbenzoyl)piperidine-1-carbonyl]phenyl}oxazolidin-2-oneYield 15%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of benzoic acid (R)-3-{4-[4-(4-chlorobenzoyl)piperidine-1-carbonyl]-3-methanesulfonylphenyl}-2-oxooxazolidin-4-ylmethyl ester (938 mg) described in Preparation Example 24, methylboronic acid (359 mg), palladium (II) acetate (34 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (123 mg) and potassium fluoride (697 mg) was added tetrahydrofuran (9 mL), and the mixture was refluxed for 8 hr. After cooling, water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was dissolved in methanol (3 mL) and 1,4-dioxane (3 mL) and 1N aqueous sodium hydroxide solution (6 mL) were added, and the mixture was stirred at room temperature for 3 hr. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (chloroform:methanol) to give the title compound (113 mg).

Workup

  1. temperaturethe mixture was refluxed for 8 hr
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with chloroform
  4. washThe organic layer was washed with saturated brine
  5. customthe solvent was evaporated
  6. dissolutionThe obtained residue was dissolved in methanol (3 mL)
  7. addition1,4-dioxane (3 mL) and 1N aqueous sodium hydroxide solution (6 mL) were added
  8. additionWater was added to the reaction mixture
  9. extractionthe mixture was extracted with chloroform
  10. washThe organic layer was washed with saturated brine
  11. customthe solvent was evaporated
  12. customThe residue was purified by column chromatography (chloroform:methanol)

Sources & evidence

ORD record
ord-eb55a505f9424761877c610b9beaebe3
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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