1-Bromopentane → (S)-1'-pentyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

HRID 1407738Notes

Reaction equation

HRID 1407738 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C@@:3]2([C:21]3[C:12](=[CH:13][C:14]4[O:19][CH2:18][CH2:17][O:16][C:15]=4[CH:20]=3)[O:11][CH2:10]2)[C:2]1=[O:22].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>O1CCOCC1>[CH2:30]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C@@:3]2([C:21]3[C:12](=[CH:13][C:14]4[O:19][CH2:18][CH2:17][O:16][C:15]=4[CH:20]=3)[O:11][CH2:10]2)[C:2]1=[O:22])[CH2:31][CH2:32][CH2:33][CH3:34]

Participants

5

Reactant 3

HCID 80571-BromopentaneHCID 10796Cesium carbonateHCID 59352191Spiro[furo[2,3-g]-1,4-benzodioxin-8(7H),3'-[3H]indol]-2'(1'H)-one, 2,3-dihydro-, (3'S)-

Product 1

HCID 59352247(S)-1'-pentyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-oneYield 72%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A suspension of (S)-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (1.0 g, 3.4 mmol), cesium carbonate (3.3 g, 10.2 mmol) and 1-bromopentane (1.02 g, 6.77 mmol) in anhydrous 1,4-dioxane (25 mL) was heated at reflux under nitrogen for 2 h. The reaction mixture was allowed to cool to ambient temperature, filtered and concentrated in vacuo. Purification of the residue by column chromatography and eluted with a 15% to 50% gradient of ethyl acetate in hexanes, followed by recrystallization from methanol afforded (S)-1′-pentyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one as an off-white solid (0.89 g, 72%): mp 111-113° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) δ7.23-7.30 (m, 1H), 7.13 (dd, J=7.4, 0.9 Hz, 1H), 7.00-7.03 (m, 1H), 6.89 (d, J=7.8 Hz, 1H), 6.46 (s, 1H), 6.19 (s, 1H), 4.73 (ABq, 2H), 4.19-4.05 (m, 4H), 3.86-3.59 (m, 2H), 1.82-1.62 (m, 2H), 1.43-1.28 (m, 4H), 0.89 (t, J=6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ177.2, 155.2, 144.5, 142.4, 138.2, 132.5, 128.7, 123.9, 123.0, 121.1, 111.4, 108.5, 99.3, 80.1, 64.5, 63.9, 58.0, 40.3, 29.0, 27.1, 22.3, 14.0; MS (ES+) m/z 366.0 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for 2 h
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by column chromatography
  6. washeluted with a 15% to 50% gradient of ethyl acetate in hexanes
  7. customfollowed by recrystallization from methanol

Sources & evidence

ORD record
ord-e23191a14d3643058a6455b8cafb4fa9
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

Loading…