Acetic Acid → (E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid diethyl amide

HRID 1072291Notes

Reaction equation

HRID 1072291 reaction equation
[H-].[Na+].C([CH:5](CC)[C:6](=[O:11])[CH2:7][C:8]([NH2:10])=[O:9])C.[CH2:14]([Li])[CH2:15]CC.[CH:19]1([C:22]2[C:31]([CH:32]=[CH:33][C:34](N(OC)C)=[O:35])=[C:30]([C:40]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=3)[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=2)[CH2:21][CH2:20]1.[C:47](O)(=O)[CH3:48].[Na+].[Cl-]>O1CCCC1.O>[CH2:14]([N:10]([CH2:47][CH3:48])[C:8](=[O:9])[CH2:7][C:6](=[O:11])[CH2:5][C:34](=[O:35])/[CH:33]=[CH:32]/[C:31]1[C:22]([CH:19]2[CH2:20][CH2:21]2)=[N:23][C:24]2[C:29]([C:30]=1[C:40]1[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH3:15]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 23617702Diethyl acetoacetamideHCID 542239083-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-N-methoxy-N-methyl-acrylamideHCID 178418339Butyllithium

Product 1

HCID 20805107(E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid diethyl amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-2.5 °C

Procedure

To a suspension of sodium hydride (600 mg, 25.0 mmol) in tetrahydrofurane (20 ml) under argon is added at −5° C. diethyl acetoacetamide (3.93 g, 25.0 mmol) in tetrahydrofurane (2.0 ml), tetrahydrofurane (22.0 ml), butyllithium (n-heptane solution, 9.2 ml, 25.0 mmol), and a solution of 3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-N-methoxy-N-methyl-acrylamide (4.51 g, 12.0 mmol) in tetrahydrofurane (40 ml). After 1 h stirring at −5 to 0° C., acetic acid (4.4 g, 73.3 mmol), 25% aq. NaCl (10 ml), and water (10 ml) are added to the reaction mixture and the mixture is stirred vigorously for 10 min. The (upper) organic phase is washed with 25% aq. NaCl (2×20 ml), the water phases are extracted with ethylacetate (25 ml) and the combined organic phases filtered and evaporated to dryness under reduced pressure. The residue is purified by silica gel chromatography (hexane/ethyl acetate 1:1) to give (E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid diethyl amide. Mp. 97-105° C., MS (ES): [M+H]+ 473.

Workup

  1. stirringthe mixture is stirred vigorously for 10 min
  2. washThe (upper) organic phase is washed with 25% aq. NaCl (2×20 ml)
  3. extractionthe water phases are extracted with ethylacetate (25 ml)
  4. filtrationthe combined organic phases filtered
  5. customevaporated to dryness under reduced pressure
  6. customThe residue is purified by silica gel chromatography (hexane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-2e94bceb73914c0d8e2cb418bedd88d7
Source dataset
uspto-grants-2005_06
Patent number
US06909003B2

Reaction notes

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