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

HRID 1072290Notes

Reaction equation

HRID 1072290 reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].C([Li])CCC.[CH:17]1([C:20]2[C:29]([CH:30]=[CH:31][C:32](N(OC)C)=[O:33])=[C:28]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=2)[CH2:19][CH2:18]1.C(O)(=O)C.[Na+].[Cl-]>O1CCCC1.O>[CH2:10]([O:9][C:3](=[O:8])[CH2:4][C:5](=[O:6])[CH2:7][C:32](=[O:33])/[CH:31]=[CH:30]/[C:29]1[C:20]([CH:17]2[CH2:18][CH2:19]2)=[N:21][C:22]2[C:27]([C:28]=1[C:38]1[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=1)=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH3:11]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 5234Sodium ChlorideHCID 8868Ethyl Acetoacetate2×HCID 24758Sodium hydride2×HCID 542239083-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-N-methoxy-N-methyl-acrylamideHCID 178418339Butyllithium2×

Product 1

HCID 11362810(E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (100 mg, 4.17 mmol) in tetrahydrofurane (4 ml) under argon is added at −5° C. ethyl acetoacetate (546 mg, 4.19 mmol), butyllithium (n-heptane solution (soln.), 1.55 ml, 4.19 mmol), and a solution of 3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-N-methoxy-N-methyl-acrylamide in tetrahydrofurane (9 ml). After 5 h stirring at room temperature, the reaction mixture is added to a suspension of sodium hydride (200 mg, 8.33 mmol), ethyl acetoacetate (1.09 g, 8.39 mmol), and butyllithium (n-heptane soln., 3.1 ml, 8.37 mmol) in tetrahydrofurane (8 ml) at −5 to 0° C. After 60 minutes at 0° C., acetic acid (100%, 2.25 g, 37.5 mmol), 25% aq. NaCl (5 ml), and water (3 ml) are added and the mixture is stirred vigorously for 10 min. The (upper) organic phase is successively washed with 25% aq. NaCl (5 ml) and water (5 ml), and evaporated to dryness under reduced pressure. The residue is dried under vacuum at 40° C. and purified by silica gel chromatography (hexane/ethyl acetate 3:1) to give (E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid ethyl ester, semisolid honey. MS (ES): [M+H]+ 446.

Workup

  1. waitAfter 60 minutes at 0° C.
  2. stirringthe mixture is stirred vigorously for 10 min
  3. washThe (upper) organic phase is successively washed with 25% aq. NaCl (5 ml) and water (5 ml)
  4. customevaporated to dryness under reduced pressure
  5. customThe residue is dried under vacuum at 40° C.
  6. custompurified by silica gel chromatography (hexane/ethyl acetate 3:1)

Sources & evidence

ORD record
ord-20fafe7a6db04e44822e6ddb1c28f8cd
Source dataset
uspto-grants-2005_06
Patent number
US06909003B2

Reaction notes

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