Sodium Bicarbonate → HCID 68515995, compound

HRID 1044460Notes

Reaction equation

HRID 1044460 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][CH:9]([CH3:11])[CH3:10])[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]([NH:8][CH:9]([CH3:11])[CH3:10])[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 87481919HCID 87481919, compound

Product 1

HCID 68515995HCID 68515995, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To a solution of n-BuLi (1.6 M in hexane, 2.22 mL, 3.56 mmol) in THF (10 mL), maintained at 0° C. under nitrogen atmosphere, hexamethyldisilazane (0.74 mL, 3.56 mmol) was added dropwise and stirred for 15 min. To this, a solution of the compound of example (59)(0.95 g, 1.78 mmol) in THF (5 mL) was added drop wise, 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 8-9. The aqueous layer was extracted with chloroform (3×50 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-isopropylamino-phenyl)-3-oxo-propionyl]-2-hydroxy-4,6-dimethoxy-phenyl}-1-methyl-pyrrolidin-2-ylmethyl ester as a brown solid (0.95 g). This ester was dissolved in conc. HCl (5 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 8-9. The aqueous layer was extracted with chloroform (3×25 mL) and washed with water (10 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2SO4, concentrated under reduced pressure and dried over vacuum to yield the compound, (+)-trans-2-(2-chloro-4-isopropylaminophenyl)-8-(2-hydroxy methyl-1-methylpyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one, as a brown solid which was taken ahead without further purification.

Workup

  1. customAt the end of 3 hrs
  2. extractionThe aqueous layer was extracted with chloroform (3×25 mL)
  3. washwashed with water (10 mL) and brine (10 mL)
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customdried over vacuum

Sources & evidence

ORD record
ord-5dd007b3b6fb487c8e7451d8f634e8d9
Source dataset
uspto-grants-2013_10
Patent number
US08563596B2

Reaction notes

Loading…