Ethanol → (3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy hept-6-enoic acid diisopropylamine salt

HRID 445949Notes

Reaction equation

HRID 445949 reaction equation
[CH:1]1([C:4]2[C:13](/[CH:14]=[CH:15]/[C@@H:16]([OH:24])[CH2:17][C@@H:18]([OH:23])[CH2:19][C:20]([OH:22])=[O:21])=[C:12]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1.CO[N-]C.C(O)C.[OH-].[Na+]>O>[CH:4]([NH:5][CH:6]([CH3:11])[CH3:7])([CH3:13])[CH3:1].[CH:1]1([C:4]2[C:13](/[CH:14]=[CH:15]/[C@@H:16]([OH:24])[CH2:17][C@@H:18]([OH:23])[CH2:19][C:20]([OH:22])=[O:21])=[C:12]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 131730687E-(7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-[(3R,5S)-3,5-dihydroxy-hept-6-enoic acid]) N-methoxy-N-methyl-amide

Product 1

HCID 60150999(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy hept-6-enoic acid diisopropylamine saltYield 186.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

E-(7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-[(3R,5S)-3,5-dihydroxy-hept-6-enoic acid])-N-methoxy-N-methyl-amide (10.3 g), ethyl alcohol (66.0 mL), and a solution of sodium hydroxide (1.4 g) in water (13.0 mL) were added to a reactor. The reaction mixture was stirred for 16 hours while maintaining the temperature of 20˜25° C., and then concentrated under reduced pressure. Ethyl acetate (53.0 mL) and water (79.0 mL) were added to the resulting residue under stirring. Ethyl acetate (53.0 mL) was added to the separated water layer, which was then adjusted to pH 3.0˜4.0 using 1N hydrochloric acid solution. The separated organic layer was concentrated under reduced pressure. Ethyl acetate (200.0 mL) and diisopropylamine (3.2 mL) were added to the resulting residue. The reaction mixture was stirred at 20˜25° C. for over 12 hours and then filtered under reduced pressure. The resulting white solid was dried under vacuum to obtain (3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy hept-6-enoic acid diisopropylamine salt (10.4 g, yield 90%).

Workup

  1. temperaturewhile maintaining the temperature of 20˜25° C.
  2. concentrationconcentrated under reduced pressure
  3. additionEthyl acetate (53.0 mL) and water (79.0 mL) were added to the resulting residue
  4. stirringunder stirring
  5. additionEthyl acetate (53.0 mL) was added to the separated water layer, which
  6. concentrationThe separated organic layer was concentrated under reduced pressure
  7. additionEthyl acetate (200.0 mL) and diisopropylamine (3.2 mL) were added to the resulting residue
  8. stirringThe reaction mixture was stirred at 20˜25° C. for over 12 hours
  9. filtrationfiltered under reduced pressure
  10. customThe resulting white solid was dried under vacuum

Sources & evidence

ORD record
ord-e747129d3a9d42caa6a3536554e4a21e
Source dataset
uspto-grants-2013_07
Patent number
US08476432B2

Reaction notes

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