Trifluoroacetic acid → 3-(7-Hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-dihydro-2H-indol-2-one

HRID 2095087Notes

Reaction equation

HRID 2095087 reaction equation
O[C:2]1([C:12]2[C:21]([OH:22])=[CH:20][C:15]3[O:16][CH2:17][CH2:18][O:19][C:14]=3[CH:13]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][C:3]1=[O:11].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[OH:22][C:21]1[C:12]([CH:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[NH:4][C:3]2=[O:11])=[CH:13][C:14]2[O:19][CH2:18][CH2:17][O:16][C:15]=2[CH:20]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 58224162HCID 58224162, compound

Product 1

HCID 469415943-(7-Hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-dihydro-2H-indol-2-oneYield 78.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-5 °C

Procedure

A 2000 L reactor was charged with dichloromethane (489.4 kg), followed by 3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-dihydro-2H-indol-2-one (92.0 kg, 307 mol) in four 23 kg portions over 1 h. The resultant solution was stirred at ambient temperature for 1 h and triethylsilane (107.2 kg, 921 mol) was added. The mixture was cooled to −5° C. and trifluoroacetic acid (105.1 kg, 921 mol) was added at a rate of 25-30 kg/h such that the temperature of the reaction mixture remained below 0° C. The mixture was stirred at −5-0° C. for 2.5 h, warmed to 18-20° C., stirred for a further 6.5 h and concentrated to dryness under reduced pressure at a temperature<30° C. Methyl tert-butyl ether (139.8 kg) was added to the residue at 15-20° C. and the mixture concentrated to near-dryness under reduced pressure at a temperature<35° C. The mixture was filtered in a centrifugal filter and a 2000 L reactor was charged with the filter cake, followed by methanol (72.7 kg). The mixture was stirred at 10-15° C. for 0.5 h and filtered in a centrifugal filter. The filter cake was dried under reduced pressure at 40-50° C. to afford 3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-dihydro-2H-indol-2-one (68.0 kg, 78%) as a colorless solid: purity (HPLC-UV at 254 nm) 99.3%.

Workup

  1. customremained below 0° C
  2. temperaturewarmed to 18-20° C.
  3. stirringstirred for a further 6.5 h
  4. concentrationconcentrated to dryness under reduced pressure at a temperature<30° C
  5. additionMethyl tert-butyl ether (139.8 kg) was added to the residue at 15-20° C.
  6. concentrationthe mixture concentrated to near-dryness under reduced pressure at a temperature<35° C
  7. filtrationThe mixture was filtered in
  8. filtrationa centrifugal filter
  9. additiona 2000 L reactor was charged with the filter cake
  10. stirringThe mixture was stirred at 10-15° C. for 0.5 h
  11. filtrationfiltered in a centrifugal filter
  12. customThe filter cake was dried under reduced pressure at 40-50° C.

Sources & evidence

ORD record
ord-abdd6b43be354a56932378a6729200de
Source dataset
uspto-grants-2013_05
Patent number
US08445696B2

Reaction notes

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