Isopropanol → HCID 118126601, compound

HRID 1752986Notes

Reaction equation

HRID 1752986 reaction equation
[P:1]([O-:43])([O-:42])([O:3][C:4](C(C)(C)C)(C(C)(C)C)[N:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:32])[C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[O:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])=[CH:7][C:6]1=[O:33])=[O:2].C(O)(C)C>C(O)(=O)C>[P:1]([OH:43])([OH:42])([O:3][CH2:4][N:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:32])[C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:20])([F:22])[F:21])=[CH:15][C:14]=2[O:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])=[CH:7][C:6]1=[O:33])=[O:2]

Participants

4

Reactant 2

HCID 3776IsopropanolHCID 131733646HCID 131733646, compound

Product 1

HCID 118126601HCID 118126601, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a 72 liter jacketed glass reactor fitted with an N2 inlet and a mechanical stirrer, and with a jacket temperature set at 40° C., was added di-tert-butyl((4-(2-(4-fluoro-2-methylphenoxy)-4-(trifluoromethyl)benzamido)-2-oxopyridin-1(2H)-yl)methyl) phosphate (20, 2820.9 g, 4.49 moles, 1.0 eq) and isopropyl alcohol (25.4 liters, 9.0 volumes). The mixture was stirred at 200 rpm, and acetic acid (14.1 liters, 5.0 volumes) was added, resulting in a clear solution. The clear solution was polish filtered and transferred to a 50 liter jacketed glass reactor system with stirring at 100 rpm. Water (5.6 liters) was added, and the jacket temperature was ramped to 71° C. over 20 minutes. After 4.5 hours of stirring and heating, HPLC analysis indicated that the reaction was complete. The jacket temperature was ramped down to 19° C. over 3 hours, and the product began crystallizing out of solution. The solid was collected by filtration, rinsed with acetone (5 liters). The solid was added back into the reactor vessel, acetone was added (8.5 liters), the jacket temperature was ramped to 45° C. over 10 minutes, and the suspension was stirred. After 40 minutes, the jacket temperature was ramped to 20° C. over 30 minutes, and the crystalline solid was collected by filtration, rinsed with acetone (5 liters) and dried in vacuo at 50° C. to give 1917.7 g (83%) of (4-(2-(4-fluoro-2-methylphenoxy)-4-(trifluoromethyl)benzamido)-2-oxopyridin-1(2H)-yl)methyl dihydrogen phosphate (9) as a crystalline white solid.

Workup

  1. customfitted with an N2 inlet and a mechanical stirrer
  2. customset at 40° C.
  3. additionwas added
  4. customresulting in a clear solution
  5. filtrationfiltered
  6. additionWater (5.6 liters) was added
  7. stirringAfter 4.5 hours of stirring
  8. temperatureheating
  9. waitThe jacket temperature was ramped down to 19° C. over 3 hours
  10. customthe product began crystallizing out of solution
  11. filtrationThe solid was collected by filtration
  12. washrinsed with acetone (5 liters)
  13. additionThe solid was added back into the reactor vessel, acetone
  14. additionwas added (8.5 liters)
  15. waitthe jacket temperature was ramped to 45° C. over 10 minutes
  16. stirringthe suspension was stirred
  17. waitAfter 40 minutes
  18. waitthe jacket temperature was ramped to 20° C. over 30 minutes
  19. filtrationthe crystalline solid was collected by filtration
  20. washrinsed with acetone (5 liters)
  21. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-3578678aa9cf41fb935d043999f34c7b
Source dataset
uspto-grants-2015_10
Patent number
US09163042B2

Reaction notes

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