Ethanol → E-7-[2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimdin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid diisopropylamine salt

HRID 445943Notes

Reaction equation

HRID 445943 reaction equation
[CH3:1][N:2]([C:7]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[C:10](/[CH:20]=[CH:21]/[C@@H:22]([OH:30])[CH2:23][C@@H:24]([OH:29])[CH2:25][C:26]([OH:28])=[O:27])=[C:9]([CH:31]([CH3:33])[CH3:32])[N:8]=1)[S:3]([CH3:6])(=[O:5])=[O:4].[CH3:34]O[N-]C.[CH2:38](O)[CH3:39].[OH-].[Na+]>O>[CH:9]([NH:8][CH:38]([CH3:39])[CH3:34])([CH3:31])[CH3:10].[CH3:1][N:2]([C:7]1[N:12]=[C:11]([C:13]2[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=2)[C:10](/[CH:20]=[CH:21]/[C@@H:22]([OH:30])[CH2:23][C@@H:24]([OH:29])[CH2:25][C:26]([OH:28])=[O:27])=[C:9]([CH:31]([CH3:33])[CH3:32])[N:8]=1)[S:3]([CH3:6])(=[O:5])=[O:4]

Participants

5

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 131730685E-(7-{2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-yl}-[(3R,5S)-3,5-dihydroxy-hept-6-enoic acid]) N-methoxy-N-methyl-amide

Product 1

HCID 11169205E-7-[2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimdin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid diisopropylamine saltYield 90%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

E-(7-{2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-yl}-[(3R,5S)-3,5-dihydroxy-hept-6-enoic acid])-N-methoxy-N-methyl-amide (38.3 g), ethyl alcohol (300.0 mL), and a solution of sodium hydroxide (5.1 g) in water (60.0 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 (240.0 mL) and water (360.0 mL) were added to the resulting residue under stirring. Ethyl acetate (240.0 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. Tetrahydrofuran (900.0 mL) and diisopropylamine (12.0 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 E-7-[2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid diisopropylamine salt (38.0 g, yield 90%, HPLC purity 99.7%).

Workup

  1. temperaturewhile maintaining the temperature of 20˜25° C.
  2. concentrationconcentrated under reduced pressure
  3. additionEthyl acetate (240.0 mL) and water (360.0 mL) were added to the resulting residue
  4. stirringunder stirring
  5. additionEthyl acetate (240.0 mL) was added to the separated water layer, which
  6. concentrationThe separated organic layer was concentrated under reduced pressure
  7. additionTetrahydrofuran (900.0 mL) and diisopropylamine (12.0 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-b0a01aff61254af8b324227d7c6fd1fe
Source dataset
uspto-grants-2013_07
Patent number
US08476432B2

Reaction notes

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