Sodium Bicarbonate → HCID 68516829, compound

HRID 1044455Notes

Reaction equation

HRID 1044455 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12](=O)[CH2:13][C:14]([C:16]1[C:17]([OH:37])=[C:18]([CH:26]2[CH2:30][CH2:29][N:28]([CH3:31])[CH:27]2[CH2:32][O:33]C(=O)C)[C:19]([O:24][CH3:25])=[CH:20][C:21]=1[O:22][CH3:23])=[O:15].C([O-])(O)=O.[Na+]>Cl>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[O:37][C:17]2[C:16]([C:14](=[O:15])[CH:13]=1)=[C:21]([O:22][CH3:23])[CH:20]=[C:19]([O:24][CH3:25])[C:18]=2[C@@H:26]1[CH2:30][CH2:29][N:28]([CH3:31])[C@H:27]1[CH2:32][OH:33]

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 87481782HCID 87481782, compound

Product 1

HCID 68516829HCID 68516829, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To a solution of n-BuLi (15% solution in hexane, 2.2 mL, 5 mmol) in THF (10 mL), maintained at 0° C. under nitrogen atmosphere, hexamethyldisilazane (1.08 mL, 5.1 mmol) was added dropwise and stirred for 15 min. To this, a solution of the compound of example (41)(1.44 g, 2.5 mmol) in THF (10 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, and basified with 10% sodium bicarbonate to pH 8 to 9. The aqueous layer was extracted with chloroform (3×25 mL). The organic layer was washed with water (25 mL), brine (25 mL) and dried over anhydrous Na2SO4. The organic layer was concentrated under reduced pressure and dried under vacuum to yield acetic acid 3-{3-[3-(2-chloro-4-trifluoromethyl-phenyl)-3-oxo-propionyl]-2-hydroxy-4,6-dimethoxy-phenyl}-1-methyl-pyrrolidin-2-ylmethyl ester as an oil (1.3 g, 90.2%). This ester was dissolved in conc. HCl (10 mL) and stirred 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 (25×3 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 compound, (+)-trans-2-(2-chloro-4-trifluoromethylphenyl)-8-(2-hydroxymethyl-1-methyl pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one as a yellow solid.

Workup

  1. customAt the end of 3 hrs
  2. extractionThe aqueous layer was extracted with chloroform (25×3 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-78be5b598c7f485b87667078bfca9775
Source dataset
uspto-grants-2013_10
Patent number
US08563596B2

Reaction notes

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