Hydrochloric Acid → (+)-trans-2-(2-Chloro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one

HRID 1363332Notes

Reaction equation

HRID 1363332 reaction equation
[H-].[Na+].[OH:3][C:4]1[C:9]([C@@H:10]2[CH2:14][CH2:13][N:12]([CH3:15])[C@H:11]2[CH2:16][OH:17])=[C:8]([O:18][CH3:19])[CH:7]=[C:6]([O:20][CH3:21])[C:5]=1[C:22](=[O:24])[CH3:23].[Cl:25][C:26]1[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=1[C:28](OC)=O.Cl>CN(C=O)C.CO>[Cl:25][C:26]1[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=1[C:28]1[O:3][C:4]2[C:5]([C:22](=[O:24])[CH:23]=1)=[C:6]([O:20][CH3:21])[CH:7]=[C:8]([O:18][CH3:19])[C:9]=2[C@@H:10]1[CH2:14][CH2:13][N:12]([CH3:15])[C@H:11]1[CH2:16][OH:17]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11895Methyl 2-chlorobenzoateHCID 24758Sodium hydrideHCID 59318484(-)-trans-1-[2-Hydroxy-3-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4,6-dimethoxyphenyl]-1-ethanone

Product 1

HCID 59318486(+)-trans-2-(2-Chloro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (50%, 2.17 g, 45.3 mmol) was added in portions to a solution of compound of example 6 (2.8 g, 9 mmol) in dry DMF (30 mL) at 0° C., under nitrogen atmosphere and with stirring. After 10 min., methyl 2-chlorobenzoate (5.09 g, 29.9 mmol) was added. The reaction mixture was stirred at 25° C. for 2 h. Methanol was added carefully below 20° C. The reaction mixture was poured over crushed ice (300 g), acidified with 1:1 HCl (pH 2) and extracted using EtOAc (2×100 mL). The aqueous layer was basified using a saturated Na2CO3 (pH 10) and extracted using CHCl3 (3×200 mL). The organic layer was dried (anhydrous Na2SO4) and concentrated. To the residue, conc. HCl (25 mL) was added and stirred at room temperature for 2 h. The reaction mixture was poured over crushed ice (300 g) and made basic using a saturated aqueous Na2CO3 solution. The mixture was extracted using CHCl3 (3×200 mL). The organic extract was washed with water, dried (anhydrous Na2SO4) and concentrated to obtain the title compound.

Workup

  1. stirringThe reaction mixture was stirred at 25° C. for 2 h
  2. additionThe reaction mixture was poured
  3. extractionextracted
  4. extractionextracted
  5. dry with materialThe organic layer was dried (anhydrous Na2SO4)
  6. concentrationconcentrated
  7. additionTo the residue, conc. HCl (25 mL) was added
  8. stirringstirred at room temperature for 2 h
  9. additionThe reaction mixture was poured
  10. customover crushed ice (300 g)
  11. extractionThe mixture was extracted
  12. extractionThe organic extract
  13. washwas washed with water
  14. dry with materialdried (anhydrous Na2SO4)
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-37dc102f7c47430e97ea60487f86fc09
Source dataset
uspto-grants-2011_02
Patent number
US07884127B2

Reaction notes

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