Hydrochloric Acid → (E)-3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-acrylic acid

HRID 1072287Notes

Reaction equation

HRID 1072287 reaction equation
[CH:1]1([C:4]2[C:13](/[CH:14]=[CH:15]/[CH:16]=[O:17])=[C:12]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1.P([O-])(O)(O)=[O:26].[Na+].OO.Cl([O-])=O.[Na+].O.O.O.O.O.S([O-])([O-])(=O)=S.[Na+].[Na+].Cl>C(#N)C.O>[CH:1]1([C:4]2[C:13](/[CH:14]=[CH:15]/[C:16]([OH:26])=[O:17])=[C:12]([C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 61475Sodium Thiosulfate PentahydrateHCID 9797032(E)-3-(2-Cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)acrylaldehydeHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphate

Product 1

HCID 22392019(E)-3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-acrylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a mixture of (E)-3-[2-Cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-propenal (50.0 g, 157.5 mmol) in acetonitrile (650 ml) and sodium dihydrogenphosphate (30.5 g, 220.5 mmol) in water (100 ml) is added hydrogen peroxide (18.8 g, 165.4 mmol) and a solution of sodium chlorite (25.0 g, 220.5 mmol) in water (120 ml) at 0° C. The reaction mixture is stirred in an ice bath for 120 min. Sodium thiosulfate pentahydrate (2.5 g, 10 mmol) and then 2M hydrochloric acid is added to adjust the pH to 2-3. After dilution with ethyl acetate (200 ml), the organic phase is separated and the pH of the aq. phase adjusted to 3-4 by addition of 2M sodium hydroxide. The reaction mixture is partitioned between ethyl acetate and water. The organic phases are separated, dried over magnesium sulphate and evaporated to afford (E)-3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-acrylic acid. MS (ES): [M−H]− 332, Mp. 173-174° C.

Workup

  1. customat 0° C
  2. customAfter dilution with ethyl acetate (200 ml), the organic phase is separated
  3. additionthe pH of the aq. phase adjusted to 3-4 by addition of 2M sodium hydroxide
  4. customThe reaction mixture is partitioned between ethyl acetate and water
  5. customThe organic phases are separated
  6. dry with materialdried over magnesium sulphate
  7. customevaporated

Sources & evidence

ORD record
ord-1cdf0c82b59c4209b0a508c03b4598df
Source dataset
uspto-grants-2005_06
Patent number
US06909003B2

Reaction notes

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