Trifluoroacetic acid → 3-(7-Hydroxy-4-methyl-3,4-dihydro-2h-1,4-benzoxazin-6-yl)-1-{[5-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2h-indol-2-one trifluoroacetate salt

HRID 1965285Notes

Reaction equation

HRID 1965285 reaction equation
C([SiH](CC)CC)C.O[C:9]1([C:29]2[C:30]([OH:40])=[CH:31][C:32]3[O:37][CH2:36][CH2:35][N:34]([CH3:38])[C:33]=3[CH:39]=2)[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([CH2:18][C:19]2[O:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=2)[C:10]1=[O:28].[F:41][C:42]([F:47])([F:46])[C:43]([OH:45])=[O:44]>>[F:41][C:42]([F:47])([F:46])[C:43]([OH:45])=[O:44].[OH:40][C:30]1[C:29]([CH:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[O:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=3)[C:10]2=[O:28])=[CH:39][C:33]2[N:34]([CH3:38])[CH2:35][CH2:36][O:37][C:32]=2[CH:31]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 685975423-hydroxy-3-(7-hydroxy-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1-{[5-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2H-indol-2-one

Product 1

HCID 866421923-(7-Hydroxy-4-methyl-3,4-dihydro-2h-1,4-benzoxazin-6-yl)-1-{[5-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2h-indol-2-one trifluoroacetate saltYield 90%

Procedure

To a cooled (0° C.) solution of triethylsilane (1.1 mL, 6.9 mmol) in trifluoroacetic acid (6.5 mL) was slowly added 3-hydroxy-3-(7-hydroxy-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1-{[5-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2H-indol-2-one (1.00 g, 2.18 mmol) portionwise as a solid. The resulting brown solution was warmed to reflux and stirred under nitrogen for 2 h. The reaction was cooled and the solvent was removed under reduced pressure. The residue was precipitated from ethyl acetate/hexanes and collected by filtration to afford 3-(7-hydroxy-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1-{[5-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2H-indol-2-one trifluoroacetate salt (1.09 g, 90%) as a light grey powder: mp 143-148° C. (hexanes); 1H NMR (300 MHz, DMSO-d6) δ8.98 (br s, 2H), 7.24-7.15 (m, 2H), 7.05-6.92 (m, 3H), 6.62 (s, 1H), 6.61 (s, 1H), 6.22 (s, 1H), 5.08 (d, J=16.7 Hz, 1H), 5.01 (d, J=16.7 Hz, 1H), 4.78 (s, 1H), 4.27-4.21 (m, 2H), 3.23-3.17 (m, 2H), 2.77 (s, 3H); MS (ES+) m/z 445.2 (M+1).

Workup

  1. temperatureThe resulting brown solution was warmed
  2. temperatureto reflux
  3. temperatureThe reaction was cooled
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was precipitated from ethyl acetate/hexanes
  6. filtrationcollected by filtration

Sources & evidence

ORD record
ord-80fe0d4693044c6cbf4c6be975e524a7
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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