Hydrochloric Acid → HCID 21113163, compound

HRID 1767139Notes

Reaction equation

HRID 1767139 reaction equation
[OH-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1/[CH:11]=[CH:12]/[CH2:13][N:14]1[CH2:17][C:16]([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])[CH2:15]1.Cl>O1CCOCC1>[F:3][C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1/[CH:11]=[CH:12]/[CH2:13][N:14]1[CH2:17][C:16]([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])[CH2:15]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 21113220HCID 21113220, compound

Product 1

HCID 21113163HCID 21113163, compoundYield 74.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

5 cm3 of a 5 N aqueous sodium hydroxide solution are added at a temperature in the region of 20° C. to 614 mg (1.267 mmol) of methyl 1-[(2E)-3-(2,5-difluorophenyl)-2-propenyl]-3-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]azetidine-3-carboxylate in solution in 20 cm3 of dioxane. After stirring under reflux for 1.5 hours, 6 cm3 of a 5 N aqueous sodium hydroxide solution are again added, and the medium is kept under reflux for another 3 hours; the reaction medium is cooled and supplemented with 4.5 cm3 of hydrochloric acid at 37%, and then concentrated to dryness under reduced pressure (2.7 kPa) to give a residue which is flash-chromatographed on a 200 cm3 column of fine silica [eluent: solvent gradient (dichloromethane-methanol-aqueous ammonia at 28%) (from 100-0-0 to 72-24-4 by volume)]. The fractions containing the product are combined and evaporated to dryness (2.7 kPa). The residue (530 mg) is taken up in 10 cm3 of dichloromethane, diluted with 25 cm3 of diethyl ether to give 445 mg of 1-[(2E)-3-(2,5-difluorophenyl)-2-propenyl]-3-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-3-azetidinecarboxylic acid in the form of a slightly pink solid melting at 211° C.

Workup

  1. temperatureunder reflux for 1.5 hours
  2. temperatureunder reflux for another 3 hours
  3. temperaturethe reaction medium is cooled
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. customto give a residue which
  6. customis flash-chromatographed on a 200 cm3 column of fine silica [eluent: solvent gradient (dichloromethane-methanol-aqueous ammonia at 28%) (from 100-0-0 to 72-24-4 by volume)]
  7. additionThe fractions containing the product
  8. customevaporated to dryness (2.7 kPa)
  9. additiondiluted with 25 cm3 of diethyl ether

Sources & evidence

ORD record
ord-c9e2f2558c2146f49d2367cac751c0f5
Source dataset
uspto-grants-2007_06
Patent number
US07232833B2

Reaction notes

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