Citric Acid → HCID 66990165, compound

HRID 454675Notes

Reaction equation

HRID 454675 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:12]=[CH:11][CH:10]=[C:9]1B(O)O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].[C:22]([O:25][C:26]1[CH:48]=[CH:47][C:46]([N:49]2[CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]2)=[CH:45][C:27]=1[C:28]([NH:30][C:31]1[CH:43]=[C:42](Br)[CH:41]=[CH:40][C:32]=1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:29])(=[O:24])[CH3:23].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C.COCCOC.O>[C:22]([O:25][C:26]1[CH:48]=[CH:47][C:46]([N:49]2[CH2:50][CH2:51][CH2:52][CH2:53][CH2:54]2)=[CH:45][C:27]=1[C:28]([NH:30][C:31]1[CH:43]=[C:42]([C:9]2[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH:12]=[CH:11][CH:10]=2)[CH:41]=[CH:40][C:32]=1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:29])(=[O:24])[CH3:23]

Participants

9

Reactant 4

HCID 311Citric AcidHCID 10340Sodium Carbonate2×HCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidHCID 66990071HCID 66990071, compound

Product 1

HCID 66990165HCID 66990165, compound

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Water (0.60 mL), 1-(tert-butoxycarbonyl)-1H-pyrrole-2-boronic acid (0.024 g), sodium carbonate (0.041 g), and bis(triphenylphosphine)palladium(II) dichloride (2.2 mg) were added to an ethylene glycol dimethyl ether (2.0 mL) solution of tert-butyl 2-(2-acetoxy-5-(piperidin-1-yl)benzamido)-4-bromobenzoate (0.080 g), followed by heating to reflux under a nitrogen atmosphere for 1 hour. The reaction mixture was cooled to room temperature, and sodium carbonate (0.016 g) was added thereto, followed by heating to reflux under a nitrogen atmosphere for 1 hour. The reaction mixture was cooled to room temperature, and a 10% aqueous solution of citric acid and ethyl acetate were added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 95-80% hexane/ethyl acetate] to obtain tert-butyl 2-(2-acetoxy-5-(piperidin-1-yl)benzamido)-4-(1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)benzoate.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 1 hour
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 1 hour
  5. temperatureThe reaction mixture was cooled to room temperature
  6. customThe organic layer was separated
  7. washwashed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 95-80% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-a6a3ef8a9f2f4525a1c93d5208bd07de
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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