Ethyl Acetate → HCID 24969673, compound

HRID 661445Notes

Reaction equation

HRID 661445 reaction equation
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[F:15][C:16]([F:32])([F:31])[C:17]1[CH:22]=[CH:21][C:20]([NH:23][C@H:24]([CH2:29][CH3:30])[CH2:25][C:26]([OH:28])=O)=[CH:19][CH:18]=1.[OH-].[Na+].C(OCC)(=O)C>CS(O)(=O)=O>[CH2:29]([C@@H:24]1[CH2:25][C:26](=[O:28])[C:19]2[C:20](=[CH:21][CH:22]=[C:17]([C:16]([F:15])([F:32])[F:31])[CH:18]=2)[NH:23]1)[CH3:30]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 14812Phosphorus oxide (P4O10)HCID 57972811HCID 57972811, compound

Product 1

HCID 24969673HCID 24969673, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6395Methanesulfonic AcidSolvent

Conditions

Temperature
70 °C

Procedure

Phosphorus pentoxide (600 g) was dissolved in methanesulfonic acid (6.0 liter) at below 40° C., the solution was added to the compound (1200 g) obtained in Example 1 (1) above and the mixture was stirred under nitrogen atmosphere at 65-75° C. for 3-4 hours. When the reaction was completed, the reaction mixture was cooled, 12N sodium hydroxide aqueous solution was added dropwise thereto at below 40° C. and the mixture was adjusted to pH 10-12. Ethyl acetate (6.0 liter) was added and the mixture was stirred, filtered and washed with ethyl acetate (6.0 liter). The filtrate was separated and the organic layer was washed with 25% ammonia water (1.8 liter) and water (1.8 liter). The organic layer was further washed with water (3.6 liter) and concentrated in vacuo at 45-55° C. of the bath temperature. The residue was dissolved in ethyl acetate (1.2 liter) and n-hexane (4.8 liter) at 50-70° C. and n-hexane (4.8 liter) was added dropwise at the same temperature. After cooled to below 10° C., the mixture was filtered and the crystalline was washed with chilled ethyl acetate/n-hexane=1/20 (1.2 liter). The wet product was air-dried or dried under reduced pressure at 45-55° C. and the titled compound was obtained (496 g, yield 44%).

Workup

  1. temperaturethe reaction mixture was cooled
  2. customat below 40° C.
  3. stirringthe mixture was stirred
  4. filtrationfiltered
  5. washwashed with ethyl acetate (6.0 liter)
  6. customThe filtrate was separated
  7. washthe organic layer was washed with 25% ammonia water (1.8 liter) and water (1.8 liter)
  8. washThe organic layer was further washed with water (3.6 liter)
  9. concentrationconcentrated in vacuo at 45-55° C. of the bath temperature
  10. dissolutionThe residue was dissolved in ethyl acetate (1.2 liter)
  11. additionn-hexane (4.8 liter) at 50-70° C. and n-hexane (4.8 liter) was added dropwise at the same temperature
  12. temperatureAfter cooled to below 10° C.
  13. filtrationthe mixture was filtered
  14. washthe crystalline was washed with chilled ethyl acetate/n-hexane=1/20 (1.2 liter)
  15. customThe wet product was air-dried
  16. customdried under reduced pressure at 45-55° C.

Sources & evidence

ORD record
ord-6ef682ff3fe741ca95a46369f8aa9186
Source dataset
uspto-grants-2011_12
Patent number
US08084611B2

Reaction notes

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