Hydrochloric Acid → 1-methyl-1'-{[5-(trifluoromethyl)furan-2-yl]methyl}-2,3-dihydro-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3'-indol]-2'(1'H)-one hydrochloride

HRID 2385168Notes

Reaction equation

HRID 2385168 reaction equation
[CH3:1][N:2]1[C:7]2[CH:8]=[C:9]3[C:14]4([C:22]5[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=5)[N:16]([CH2:23][C:24]5[O:25][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:28]=5)[C:15]4=[O:33])[CH2:13][O:12][C:10]3=[CH:11][C:6]=2[O:5][CH2:4][CH2:3]1.[ClH:34].O1CCOCC1>CO>[ClH:34].[CH3:1][N:2]1[C:7]2[CH:8]=[C:9]3[C:14]4([C:22]5[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=5)[N:16]([CH2:23][C:24]5[O:25][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:28]=5)[C:15]4=[O:33])[CH2:13][O:12][C:10]3=[CH:11][C:6]=2[O:5][CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 461955661-methyl-1'-{[5-(trifluoromethyl)furan-2-yl]methyl}-2,3-dihydro-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3'-indol]-2'(1'H)-one

Product 1

HCID 461955651-methyl-1'-{[5-(trifluoromethyl)furan-2-yl]methyl}-2,3-dihydro-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3'-indol]-2'(1'H)-one hydrochlorideYield 94%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Following the procedure as described in EXAMPLE 2 and making non-critical variations using 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 to replace 1-(diphenylmethyl)-3-(2-hydroxy-4-methoxy-5-methylphenyl)-1,3-dihydro-2H-indol-2-one, 1-methyl-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}-2,3-dihydro-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3′-indol]-2′(1′H)-one was obtained. To a suspension of 1-methyl-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}-2,3-dihydro-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3′-indol]-2′(1′H)-one (0.59 g, 1.3 mmol) in methanol (8.5 mL) was added 4 M hydrochloric acid in 1,4-dioxane (1.5 mL, 6.0 mmol) and the resulting solution was stirred at ambient temperature for 35 min. The solvent was removed and the residue was dried under reduced pressure. The residue was then precipitated by addition of hexanes, sonicated and the solvent was removed under reduced pressure. This process was repeated several times, until the solid formed a fine suspension in hexanes. The material was then collected by filtration and air-dried to afford 1-methyl-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}-2,3-dihydro-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3′-indol]-2′(1′H)-one hydrochloride (0.60 g, 94%) as a pale gray powder: mp 105° C. (dec.) (hexanes); 1H NMR (300 MHz, DMSO-d6) δ7.33 (ddd, J=7.8, 7.5, 0.9 Hz, 1H), 7.22-7.17 (m, 3H), 7.07 (dd, J=7.5, 7.5 Hz, 1H), 6.74 (d, J=3.3 Hz, 1H), 6.48 (s, 1H), 6.25-6.19 (m, 1H), 5.10 (d, J=16.2 Hz, 1H), 5.02 (d, J=16.2 Hz, 1H), 4.76 (d, J=9.3 Hz, 1H), 4.65 (d, J=9.3 Hz, 1H), 4.33-4.22 (m, 2H), 3.27-3.18 (m, 2H), 2.68 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ176.4, 157.2, 153.2, 147.9, 141.9, 139.6 (q, J=42.0 Hz), 131.3, 129.0, 123.9, 123.4, 121.5, 119.0 (q, J=267 Hz), 114.2 (q, J=2.8 Hz), 112.4, 109.9, 109.3, 98.8, 79.9, 62.7, 57.1, 48.8, 48.6, 41.5, 36.6; MS (ES+) m/z 457.1 (M+1); Anal. Calcd. for C24H19FN2O4.HCl: C, 58.49; H, 4.09; N, 5.68. Found: C, 58.85; H, 3.74; N, 5.37.

Workup

  1. customThe solvent was removed
  2. customthe residue was dried under reduced pressure
  3. customThe residue was then precipitated by addition of hexanes
  4. customsonicated
  5. customthe solvent was removed under reduced pressure
  6. customuntil the solid formed a fine suspension in hexanes
  7. filtrationThe material was then collected by filtration
  8. customair-dried

Sources & evidence

ORD record
ord-1c11bbbda83c46a0bce524117e7b06b1
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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