Sodium Bicarbonate → HCID 68513538, compound

HRID 1044463Notes

Reaction equation

HRID 1044463 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:11](=O)[CH2:12][C:13]([C:15]1[C:16]([OH:36])=[C:17]([CH:25]2[CH2:29][CH2:28][N:27]([CH3:30])[CH:26]2[CH2:31][O:32]C(=O)C)[C:18]([O:23][CH3:24])=[CH:19][C:20]=1[O:21][CH3:22])=[O:14].C([O-])(O)=O.[Na+]>Cl>[Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:11]1[O:36][C:16]2[C:15]([C:13](=[O:14])[CH:12]=1)=[C:20]([O:21][CH3:22])[CH:19]=[C:18]([O:23][CH3:24])[C:17]=2[C@@H:25]1[CH2:29][CH2:28][N:27]([CH3:30])[C@H:26]1[CH2:31][OH:32]

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 87480783HCID 87480783, compound

Product 1

HCID 68513538HCID 68513538, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To a solution of n-BuLi (15% in hexane, 2.54 mL, 5.8 mmol) in THF (25 mL), maintained at 0° C. under nitrogen atmosphere, hexamethyldisilazane (1.25 mL, 5.8 mmol) was added dropwise and stirred for 15 min. To this, a solution of (−)-trans-2-chloro-4-nitro-benzoic acid 2-(2-acetoxymethyl-1-methyl-pyrrolidin-3-yl)-6-acetyl-3,5-dimethoxy-phenyl ester (1.6 g, 3 mmol) in THF (25 mL) was added dropwise, maintaining the temperature at 0° C. After the addition, the reaction was allowed to warm to room temperature and stirred for 2.5 hrs. The reaction mixture was acidified with dilute HCl, basified with 10% NaHCO3 solution to pH 8 to 9. The aqueous layer was extracted with chloroform (3×50 mL). The organic layer was washed with water (25 mL), brine (25 mL), dried over anhydrous Na2SO4. The organic layer was concentrated under reduced pressure and under vacuum to yield acetic acid 3-{3-[3-(2-chloro-4-nitro phenyl)-3-oxopropionyl]-2-hydroxy-4,6-dimethoxyphenyl}-1-methylpyrrolidin-2-ylmethyl ester as a yellow solid (1.6 g). This ester was dissolved in conc. HCl (16 mL) and stirred at room temperature for 3 hrs to effect cyclisation. At the end of 3 hrs, the reaction mixture was basified with solid NaHCO3 to pH 8 to 9. The aqueous layer was extracted with chloroform (3×50 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over anhydrous Na2SO4, concentrated under reduced pressure and dried over vacuum. The residue was purified by column chromatography with 3% methanol in chloroform and 0.1% ammonia as eluent to yield the title compound as a yellow solid.

Workup

  1. customAt the end of 3 hrs
  2. extractionThe aqueous layer was extracted with chloroform (3×50 mL)
  3. washwashed with water (25 mL) and brine (25 mL)
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customdried over vacuum
  7. customThe residue was purified by column chromatography with 3% methanol in chloroform and 0.1% ammonia as eluent

Sources & evidence

ORD record
ord-578f5daea7ea4a4aa71f6835dd573d9c
Source dataset
uspto-grants-2013_10
Patent number
US08563596B2

Reaction notes

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