Cesium carbonate → HCID 51357549, compound

HRID 2095089Notes

Reaction equation

HRID 2095089 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:29][C:30]1[O:31][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:33][CH:34]=1>CC(C)=O>[F:36][C:35]([F:38])([F:37])[C:32]1[O:31][C:30]([CH2:29][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]3([C:13]4=[CH:14][C:15]5[O:19][CH2:18][O:17][C:16]=5[CH:20]=[C:12]4[O:11][CH2:10]3)[C:2]2=[O:21])=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27946052-(Bromomethyl)-5-(trifluoromethyl)furanHCID 53375495spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

Product 1

HCID 51357549HCID 51357549, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
25 °C

Procedure

A 100 L reactor was charged with spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (6.03 kg, 19.5 mol), followed by cesium carbonate (16.02 kg, 48.7 mol). Acetone (48.8 kg) was added and the resultant suspension was heated to reflux over 1 h. 2-Bromomethyl-5-(trifluoromethyl)furan (4.92 kg, 21.2 mol) was added by means of an addition funnel over a period of 2 h while the reaction mixture was maintained at reflux. The reaction mixture was stirred at reflux for a further 2 h and the acetone was removed by distillation at atmospheric pressure until 37 L of distillate had been collected. Toluene (48.8 kg) was added and the distillation was continued, first at atmospheric pressure then under reduced pressure until 37 L of distillate had been collected. Toluene (36.9 kg) was added and the distillation was continued at 54-55° C. and a pressure of 150-180 mbar until 37 L of distillate had been collected. The contents of the 100 L reactor were allowed to cool to 25° C. and toluene (40.9 kg) was added. The contents of the 100 L reactor were transferred to a 200 L reactor and deionized water (48.8 kg) was added. The stirred mixture was warmed to 39° C., the stirring was stopped and the phases were allowed to separate for 11 h. The lower phase was removed and the remaining toluene phase was subjected to distillation at 55-64° C. under a reduced pressure of 100 mbar until 18 L of distillate had been collected. The resultant solution was diluted with toluene to a total volume of 98 L. The contents of the 200 L reactor were passed through a chromatography column packed with silica gel (20 kg) and toluene (40 kg). The column was eluted with toluene such that ten 30 kg fractions were collected. The column was washed with acetone (100 kg). Fractions 2 through 10 were successively transferred to a 200 L reactor as a distillation under reduced pressure was proceeding. The contents of the reactor were adjusted with toluene to a volume of 50 L and the solution was heated to 79° C. Heptane (85 kg) was added over 15 minutes and the mixture was cooled to 10° C. over a period of 3 h. Crystallization started at an internal temperature of 56° C. The solid was collected by filtration, washed with a mixture of heptane (10.2 kg) and toluene (5.1 kg) and dried at 45-50° C. under a reduced pressure of 50 mbar over a period of 15 h to afford 1′-{[5-(trifluoromethyl)-2-furyl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (6.08 kg, 73%) as a colorless solid: purity (HPLC-UV at 230 nm) 99.6%; mp 139-141° C.; 1H NMR (300 MHz, CDCl3) δ7.32-6.97 (m, 5H), 6.72 (d, J=3.3 Hz, 1H), 6.66 (s, 1H), 6.07 (s, 1H), 5.90-5.88 (m, 2H), 5.05, 4.86 (ABq, JAB=16.1 Hz, 2H), 4.91 (d, J=9.0 Hz, 1H), 4.66 (d, J=9.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 176.9, 155.7, 153.5, 148.8, 142.2, 141.9, 140.8, 140.2, 139.7, 139.1, 132.1, 129.2, 124.7, 124.1, 123.7, 121.1, 120.1, 117.6, 114.5, 114.4, 110.3, 109.7, 103.0, 101.9, 93.8, 80.0, 57.8, 36.9; MS (ES+) m/z 430.2 (M+1), 452.2 (M+23); Calc'd for C22H14F3NO5: C, 61.54%; H, 3.29%; N, 3.26%. Found: C, 61.51%; H, 3.29%; N, 3.26%.

Workup

  1. temperatureto reflux over 1 h
  2. temperaturewas maintained
  3. temperatureat reflux
  4. temperatureat reflux for a further 2 h
  5. customthe acetone was removed by distillation at atmospheric pressure until 37 L of distillate
  6. customhad been collected
  7. additionToluene (48.8 kg) was added
  8. distillationthe distillation
  9. distillationunder reduced pressure until 37 L of distillate had been collected
  10. additionToluene (36.9 kg) was added
  11. distillationthe distillation
  12. customwas continued at 54-55° C.
  13. distillationa pressure of 150-180 mbar until 37 L of distillate had been collected
  14. additiontoluene (40.9 kg) was added
  15. customThe contents of the 100 L reactor were transferred to a 200 L reactor
  16. additiondeionized water (48.8 kg) was added
  17. temperatureThe stirred mixture was warmed to 39° C.
  18. customto separate for 11 h
  19. customThe lower phase was removed
  20. distillationthe remaining toluene phase was subjected to distillation at 55-64° C. under a reduced pressure of 100 mbar until 18 L of distillate
  21. customhad been collected
  22. additionThe resultant solution was diluted with toluene to a total volume of 98 L
  23. washThe column was eluted with toluene such that ten 30 kg fractions
  24. customwere collected
  25. washThe column was washed with acetone (100 kg)
  26. distillationFractions 2 through 10 were successively transferred to a 200 L reactor as a distillation under reduced pressure
  27. temperaturethe solution was heated to 79° C
  28. additionHeptane (85 kg) was added over 15 minutes
  29. temperaturethe mixture was cooled to 10° C. over a period of 3 h
  30. customCrystallization
  31. customstarted at an internal temperature of 56° C
  32. filtrationThe solid was collected by filtration
  33. washwashed with a mixture of heptane (10.2 kg) and toluene (5.1 kg)
  34. customdried at 45-50° C. under a reduced pressure of 50 mbar over a period of 15 h

Sources & evidence

ORD record
ord-83c5d3b403b648a8a1344092ab9fb1bf
Source dataset
uspto-grants-2013_05
Patent number
US08445696B2

Reaction notes

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