Hydrochloric Acid → HCID 69345775, compound

HRID 1767138Notes

Reaction equation

HRID 1767138 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]=[CH:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][C:14]([CH2:22][CH2:23][CH2:24][C:25]2[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][C:26]=2[F:37])([C:18]([O:20]C)=[O:19])[CH2:13]1.CO.[OH-].[Na+].Cl>O1CCOCC1.ClCCl.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]=[CH:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][C:14]([CH2:22][CH2:23][CH2:24][C:25]2[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][C:26]=2[F:37])([C:18]([OH:20])=[O:19])[CH2:13]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 69345731HCID 69345731, compound

Product 1

HCID 69345775HCID 69345775, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 0.21 g of the enantiomer B of methyl 4-[3-(2,5-difluorophenyl)-2-propenyl]-2-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-2-morpholine-carboxylate in a mixture of 10 cm3 of 1,4-dioxane, 10 cm3 of methanol and 1.22 cm3 of 5 N sodium hydroxide is heated at a temperature in the region of 80° C. with stirring and under an inert atmosphere for 12 hours. After cooling to about 20° C., the reaction medium is evaporated under reduced pressure (2 kPa; 45° C.) to give a whitish crust. The residue is taken up in 25 cm3 of dichloromethane and 10 cm3 of distilled water and then neutralized with 1.2 cm3 of 5 N hydrochloric acid. The organic phase is dried over magnesium sulfate, filtered and then evaporated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C. The residue obtained is purified by chromatography on a silica gel column (particle size 70–200 μm; diameter 2 cm), eluting with a mixture of chloroform-methanol-aqueous ammonia (28%) (12/3/0.5 by volume) and collecting 10 cm3 fractions. The fractions containing the expected product are combined and then evaporated according to the conditions described above. 0.14 g of the enantiomer B of 4-[3-(2,5-difluorophenyl)-2-propenyl]-2-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-2-morpholinecarboxylic acid is obtained in the form of a thick orange oil.

Workup

  1. temperatureAfter cooling to about 20° C.
  2. customthe reaction medium is evaporated under reduced pressure (2 kPa; 45° C.)
  3. customto give a whitish crust
  4. dry with materialThe organic phase is dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C
  7. customThe residue obtained
  8. customis purified by chromatography on a silica gel column (particle size 70–200 μm; diameter 2 cm)
  9. washeluting with a mixture of chloroform-methanol-aqueous ammonia (28%) (12/3/0.5 by volume)
  10. customcollecting 10 cm3 fractions
  11. additionThe fractions containing the expected product
  12. customevaporated

Sources & evidence

ORD record
ord-651753ba0430409ca44f29ff8fdad399
Source dataset
uspto-grants-2007_06
Patent number
US07232833B2

Reaction notes

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