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 2385012Notes

Reaction equation

HRID 2385012 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-11ee48122c134eaaa6c42a34f402d2e7
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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