Cesium carbonate → 6-bromo-1'-((5-(trifluoromethyl)furan-2-yl)methyl)-2H-spiro[benzofuran-3,3'-indolin]-2'-one

HRID 2384955Notes

Reaction equation

HRID 2384955 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][C:18]3[O:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=3)[C:9]2=[O:27])=[C:4]([OH:28])[CH:3]=1.Cl[CH2:30]I.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3([CH2:30][O:28][C:4]=2[CH:3]=1)[C:16]1[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=1)[N:10]([CH2:17][C:18]1[O:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=1)[C:9]3=[O:27]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11644ChloroiodomethaneHCID 673571633-(4-Bromo-2-hydroxyphenyl)-1-((5-(trifluoromethyl)furan-2-yl)methyl)indolin-2-one

Product 1

HCID 461941796-bromo-1'-((5-(trifluoromethyl)furan-2-yl)methyl)-2H-spiro[benzofuran-3,3'-indolin]-2'-oneYield 78.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-(4-bromo-2-hydroxyphenyl)-1-{[5-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2H-indol-2-one (4.3 g, 9.5 mmol), chloroiodomethane (1.8 mL, 25.3 mmol) in tetrahydrofuran (100 mL) was added cesium carbonate (9.9 g, 30.5 mmol) under Argon. The mixture was stirred at ambient temperature for 16 h, then filtered through a pad of celite. The filtrate was concentrated under vacuum. The residue was treated with diethyl ether/hexanes to afford 6-bromo-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (3.46 g, 78%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ7.30 (td, J=7.9, 1.5 Hz, 1H), 7.16-7.03 (m, 3H), 6.69 (d, J=7.9 Hz, 1H), 6.93 (dd, J=8.2, 1.8 Hz, 1H), 6.77-6.71 (m, 1H), 6.53 (d, J=8.2 Hz, 1H), 6.42-6.37 (m, 1H), 5.06 (d, J=16.1 Hz, 1H), 4.97 (d, J=9.4 Hz, 1H), 4.86 (d, J=16.1 Hz, 1H), 4.71 (d, J=9.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ176.5, 161.5, 151.8, 141.4, 131.6, 129.3, 128.0, 124.5 (d), 124.0, 114.2, 112.6 (d), 109.2 (d), 80.1, 57.5, 36.9; MS (ES+) m/z 463.9 (M+1), 465.9 (M+1).

Workup

  1. filtrationfiltered through a pad of celite
  2. concentrationThe filtrate was concentrated under vacuum
  3. additionThe residue was treated with diethyl ether/hexanes

Sources & evidence

ORD record
ord-40f93b85d6cf4d5abe22c7c682a666f9
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

Loading…