Sodium Hydroxide → 147696-46-6

HRID 1384785Notes

Reaction equation

HRID 1384785 reaction equation
P([O-])(O)(O)=O.[K+].[OH-].[Na+].[C:9]([C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:32])[C:25]([OH:31])([CH3:30])[C:26]([F:29])([F:28])[F:27])=[CH:19][CH:18]=1)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CC(OC)(C)C>[C:9]([C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:32])[C@@:25]([OH:31])([CH3:30])[C:26]([F:27])([F:28])[F:29])=[CH:19][CH:18]=1)(=[O:16])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 14798Sodium Hydroxide2×HCID 516951Monobasic potassium phosphateHCID 21183546N-(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide

Product 1

HCID 177852147696-46-6

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
38 °C

Procedure

5 mM potassium dihydrogen phosphate solution (50 mL) was adjusted to pH 7.1 with 0.1 N sodium hydroxide solution (2 mL), porcine pancreatic lipase (Biocatalysts, Treforest, UK) (0.2 g) added and the pH again adjusted to 7.1 with 0.1 N sodium hydroxide solution (2 mL). Racemic butyric ester derived from N-(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide (1 g) was dissolved in MTBE (10 mL) and added to the reaction, washing in with further MTBE (2 mL). The reaction was stirred at 38° C. under pH control initially set at 7.05 max/7.00 min. After 24 hr., further porcine pancreatic lipase (0.8 g) was added and the pH adjusted to 7.55 max/7.50 min and left for a further 42 hours when a total of 10 mL of 0.1 N sodium hydroxide had been added. The reaction mixture was acidified to pH 3.5 with 2 N HCl (2 mL), stirred for 15 min., then ethyl acetate (30 mL) was added and the mixture was stirred for a further 10 min. The mixture was then filtered and the residue washed with ethyl acetate (20 mL). The aqueous phase was separated and extracted with ethyl acetate (30 mL). The combined organic extracts were washed with 50% brine (20 mL), filtered and evaporated to an oil which partly crystallized. Yield: 0.95 g. The product was a mixture of the (R)-alcohol (99% enantiomeric excess) and ester.

Workup

  1. additionadded
  2. additionadded to the reaction
  3. washwashing in with further MTBE (2 mL)
  4. custominitially set at 7.05 max/7.00 min
  5. addition, further porcine pancreatic lipase (0.8 g) was added
  6. customadjusted to 7.55 max/7.50 min
  7. waitleft for a further 42 hours when a total of 10 mL of 0.1 N sodium hydroxide
  8. additionhad been added
  9. stirringstirred for 15 min.
  10. additionethyl acetate (30 mL) was added
  11. stirringthe mixture was stirred for a further 10 min
  12. filtrationThe mixture was then filtered
  13. washthe residue washed with ethyl acetate (20 mL)
  14. customThe aqueous phase was separated
  15. extractionextracted with ethyl acetate (30 mL)
  16. washThe combined organic extracts were washed with 50% brine (20 mL)
  17. filtrationfiltered
  18. customevaporated to an oil which
  19. custompartly crystallized
  20. additiona mixture of the (R)-alcohol (99% enantiomeric excess) and ester

Sources & evidence

ORD record
ord-dc660c8dae474442a11e9b25b6e98eb6
Source dataset
uspto-grants-2001_07
Patent number
US06261830B1

Reaction notes

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