Sodium Hydroxide → (4S)-3-[(5S)-5-(4-Fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one

HRID 2282089Notes

Reaction equation

HRID 2282089 reaction equation
O=[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]1[C@H:8]1[CH2:12][O:11][CH2:10][N:9]1[C:13](=[O:26])[CH2:14][CH2:15][CH2:16][C:17]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)=[O:18].[O:27]=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].S([O-])([O-])(=O)=O.[Mg+2].[OH-].[Na+]>O.C1(C)C=CC=CC=1>[F:25][C:22]1[CH:23]=[CH:24][C:19]([C@@H:17]([OH:18])[CH2:16][CH2:15][CH2:14][C:13]([N:9]2[C@@H:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:2]=3)[CH2:12][O:11][C:10]2=[O:27])=[O:26])=[CH:20][CH:21]=1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 62657Potassium Phosphate, TribasicHCID 107526(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanalHCID 67258465HCID 67258465, compound

Product 1

HCID 10269700(4S)-3-[(5S)-5-(4-Fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To the resin kettle is charged 5-((4S)-2-oxo-4-phenyl(1,3-oxazolidin-3-yl))-1-(4-fluorophenyl)pentane-1,5-dione (120 g) as a powder, followed by dextrose powder (91 g), toluene (200 ml), and buffer (750 ml of 0.02M potassium phosphate and 0.002 M Magnesium sulfate). The head plate is fitted and dogged down. All appropriate ports are closed except for the pH probe port which is fitted with the pH probe. The motor is then fitted to the coupling and stirring is initiated to a rate of 1200 rpm. The pH of the reaction mixture is measured and adjusted to 7.0+0.1. The temperature of the reaction mixture is brought to 30+1° C. While the reaction is brought to temperature, 0.4 g Na-NADP, 0.8 g GDH, and 2.00 g of lyophilized KRED were dissolved in 40 ml of de-ionized water. When the reactor temperature is in the appropriate range, the enzyme suspension is added in one portion while stirring. The titration program is started and the pH is maintained at 7.0+/−0.1 for the duration of the reaction by addition of 4N NaOH. The reaction is stirred at 30° C. for 16 hr. The reactor is sampled periodically and checked for substrate conversion by HPLC as described in Example 4. Periodic sampling and analysis is continued until the conversion reaches 99% or better.

Workup

  1. customThe head plate is fitted
  2. customAll appropriate ports are closed except for the pH probe port which
  3. customis fitted with the pH probe
  4. customThe motor is then fitted to the coupling
  5. custom1° C
  6. additionthe enzyme suspension is added in one portion
  7. stirringwhile stirring
  8. stirringThe reaction is stirred at 30° C. for 16 hr
  9. aliquotThe reactor is sampled periodically
  10. aliquotPeriodic sampling

Sources & evidence

ORD record
ord-580ed9b5e66444bda665f29a2af74978
Source dataset
uspto-grants-2015_09
Patent number
US09139820B2

Reaction notes

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