Sodium Carbonate → HCID 86674902, compound

HRID 1184721Notes

Reaction equation

HRID 1184721 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].CO[C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)=[O:26].[C:36]([O-])([O-])=[O:37].[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]([CH:32]4[CH:31]=[CH:30][C:29]([O:37][CH3:36])=[CH:28][C:27]4=[C:25]=[O:26])[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 27343694-Methoxycarbonylphenylboronic acidHCID 679732624-(5-Bromo-2,3-dihydro-benzofuran-2-yl)-piperidine-1-carboxylic acid isopropyl ester

Product 1

HCID 86674902HCID 86674902, compound

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 (1.70 g), 4-(methoxycarbonyl)phenyl boronic acid (997 mg), in N,N-dimethylformamide (50 mL) a 2 M aqueous Na2CO3 solution (5.77 mL) is added. The mixture is sparged with argon for 10 min and PdCl2[1,1′-bis(diphenylphosphino)-ferrocene]*CH2Cl2 complex (377 mg) is added. The resulting mixture is stirred for 3 h at 90° C. After cooling to room temperature, water is added and the aqueous phase is extracted with ethyl acetate. The organic phase is concentrated and the residue is purified by HPLC on reversed phase (MeOH/H2O/TFA) yielding 4-[5-(4-methoxy-carbonyl-phenyl)-2,3-dihydro-benzofuran-2-yl]-piperidine-1-carboxylic acid isopropyl ester. The material was mixed with methanol (20 mL) and 1 M aqueous sodium hydroxide (11.5 mL). After heating for 5 h to 55° C. the mixture was cooled to 20° C. and acidified with 1 M aqueous HCl. The precipitate formed was filtered off, washed with water and dried in vacuo. LC (method 5): tR=1.59 min; Mass spectrum (ESI+): m/z=410 [M+H]+.

Workup

  1. customThe mixture is sparged with argon for 10 min
  2. additionPdCl2[1,1′-bis(diphenylphosphino)-ferrocene]*CH2Cl2 complex (377 mg) is added
  3. temperatureAfter cooling to room temperature
  4. additionwater is added
  5. extractionthe aqueous phase is extracted with ethyl acetate
  6. concentrationThe organic phase is concentrated
  7. customthe residue is purified by HPLC on reversed phase (MeOH/H2O/TFA)

Sources & evidence

ORD record
ord-7df556cb9c6e4003b7fb41a9e85612dd
Source dataset
uspto-grants-2014_03
Patent number
US08669271B2

Reaction notes

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