Hydrochloric Acid → HCID 21113170, compound

HRID 1767136Notes

Reaction equation

HRID 1767136 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[S:9][CH2:10][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[S:9][CH2:10][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 21113230HCID 21113230, compound

Product 1

HCID 21113170HCID 21113170, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 0.22 g of the enantiomer B of methyl 4-[2-[(2,5-difluorophenyl)thio]ethyl]-2-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-2-morpholinecarboxylate in a mixture of 10 cm3 of 1,4-dioxane, 10 cm3 of methanol and 1.23 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 and extracted with 25 cm3 of diethyl ether. 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 chloroform-methanol-aqueous ammonia (28%) (12/3/0.5 by volume) mixture and collecting 10 cm3 fractions. The fractions containing the expected product are combined and then evaporated according to the conditions described above. 0.2 g of the enantiomer B of 4-[2-[(2,5-difluorophenyl)thio]ethyl]-2-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-2-morpholinecarboxylic acid is obtained in the form of a white solid.

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. extractionextracted with 25 cm3 of diethyl ether
  5. dry with materialThe organic phase is dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C
  8. customThe residue obtained
  9. customis purified by chromatography on a silica gel column (particle size 70–200 μm; diameter 2 cm)
  10. washeluting with a chloroform-methanol-aqueous ammonia (28%) (12/3/0.5 by volume) mixture
  11. customcollecting 10 cm3 fractions
  12. additionThe fractions containing the expected product
  13. customevaporated

Sources & evidence

ORD record
ord-891a878e0331400488839911dba76150
Source dataset
uspto-grants-2007_06
Patent number
US07232833B2

Reaction notes

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