Sodium Chloride → (1S)-[(2R)-(2,4-difluorophenyl)-2-oxiranyl]ethanol

HRID 368901

Reaction equation

HRID 368901 reaction equation
C([C@@H:6]([C@H:8]([C:10]([O:12][CH2:13]C)=O)[OH:9])O)(OCC)=O.C(OO)(C)(C)C.[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1C(=C)[C@@H](O)C.[OH-].[Na+].[Na+].[Cl-].[O-]S([O-])(=O)=O.[Mg+2]>C(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[C@:10]1([O:12][CH2:13]1)[C@@H:8]([OH:9])[CH3:6]

Participants

9

Reactant 6

HCID 5234Sodium ChlorideHCID 6410tert-Butyl hydroperoxideHCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 6993580Diethyl tartrateHCID 15130435(2S)-3-(2,4-Difluorophenyl)-3-buten-2-ol

Product 1

HCID 10631861(1S)-[(2R)-(2,4-difluorophenyl)-2-oxiranyl]ethanolYield 393.3%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-5 °C

Procedure

To a solution of diethyl L(+)-tartrate (161 ml, 0.94 mole) in dry CH2Cl2 (24 L) was added activated 3A° molecular sieve powder (600 g) and cooled the mixture to -5° C. Added a solution of titanium (IV) isopropoxide (597 ml, 2.0 mole) followed by t-butyl hydroperoxide (1.56 L of 5-6M solution in decane) and continue to stir at -5° C. for 25 minutes. To this mixture, a solution of crude 6a, (664 g) in CH2Cl2 (2 L) was added and stirred for 12 hours at 5° C. Cooled the reaction mixture to -40° C., added 1.4 L of 30% aq. NaOH solution saturated with NaCl and the mixture was allowed to warm to 10° C. Added 1.2 kg of MgSO4, 400 g of celite and continued to stir at 10° C. for 30 minutes. The mixture was suction-filtered over celite. To the filtrate toluene (20 L), and 15 L of ether were added and insoluble material removed by filtration. The filtrate was evaporated under reduced pressure to give the crude 7a as a light brown oil (740 g).

Workup

  1. stirringstirred for 12 hours at 5° C
  2. temperatureCooled the reaction mixture to -40° C.
  3. temperatureto warm to 10° C
  4. stirringto stir at 10° C. for 30 minutes
  5. filtrationThe mixture was suction-filtered over celite
  6. additionTo the filtrate toluene (20 L), and 15 L of ether were added
  7. custominsoluble material removed by filtration
  8. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-007c59cd1045405dba9cea606c3c1507
Source dataset
uspto-grants-2000_10
Patent number
US06133485

Linked notes

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