Sodium Carbonate → 4-[5-(4-Methanesulfonyl-phenyl)-2,3-dihydro-benzofuran-2-yl]-piperidine-1-carboxylic acid isopropyl ester

HRID 1184723Notes

Reaction equation

HRID 1184723 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([CH:13]2[CH2:17][C:16]3[CH:18]=[C:19](Br)[CH:20]=[CH:21][C:15]=3[O:14]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[CH3:23][S:24]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)(=[O:26])=[O:25].C([O-])([O-])=O.[Na+].[Na+]>CN(C)C=O>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([CH:13]2[CH2:17][C:16]3[CH:18]=[C:19]([C:30]4[CH:31]=[CH:32][C:27]([S:24]([CH3:23])(=[O:26])=[O:25])=[CH:28][CH:29]=4)[CH:20]=[CH:21][C:15]=3[O:14]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 679732624-(5-Bromo-2,3-dihydro-benzofuran-2-yl)-piperidine-1-carboxylic acid isopropyl ester

Product 1

HCID 573891414-[5-(4-Methanesulfonyl-phenyl)-2,3-dihydro-benzofuran-2-yl]-piperidine-1-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 4-(5-bromo-2,3-dihydro-benzofuran-2-yl)-piperidine-1-carboxylic acid isopropyl ester (200 mg) and 4-(methanesulfonyl)phenylboronic acid (119 mg) in N,N-dimethylformamide (2 mL) a 2 M aqueous Na2CO3 solution (0.68 mL) is added. The mixture is sparged with argon for 10 min and PdCl2[1,1′-bis(diphenylphosphino)-ferrocene]*CH2Cl2 complex (44 mg) is added. The resulting mixture is stirred over night at 90° C. After cooling to room temperature, water (20 mL) is added and the mixture is extracted three times with ethyl acetate. The organic phase is dried (Na2SO4) and the solvent is evaporated. The residue is chromatographed on silica gel (ethyl acetate/cyclohexane 1:22:1) to give the title compound. Yield: 149 mg (62% of theory); LC (method 1): tR=1.29 min; Mass spectrum (ESI+): m/z=444 [M+H]+.

Workup

  1. additionis added
  2. customThe mixture is sparged with argon for 10 min
  3. additionPdCl2[1,1′-bis(diphenylphosphino)-ferrocene]*CH2Cl2 complex (44 mg) is added
  4. temperatureAfter cooling to room temperature
  5. additionwater (20 mL) is added
  6. extractionthe mixture is extracted three times with ethyl acetate
  7. dry with materialThe organic phase is dried (Na2SO4)
  8. customthe solvent is evaporated
  9. customThe residue is chromatographed on silica gel (ethyl acetate/cyclohexane 1:22:1)

Sources & evidence

ORD record
ord-2f773a2895804b948a06125a537ac4cb
Source dataset
uspto-grants-2014_03
Patent number
US08669271B2

Reaction notes

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