Sodium hydride → methyl 4-[(2'-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-1'(2'H)-yl)methyl]benzoate

HRID 1965663Notes

Reaction equation

HRID 1965663 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].[H-].[Na+].Br[CH2:26][C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=1>O1CCCC1>[O:22]=[C:2]1[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:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]1[CH2:26][C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 256687Methyl 4-(bromomethyl)benzoate2×HCID 58224164Spiro[furo[2,3-g]-1,4-benzodioxin-8(7H),3'-[3H]indol]-2'(1'H)-one, 2,3-dihydro

Product 1

HCID 46194858methyl 4-[(2'-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-1'(2'H)-yl)methyl]benzoateYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (3.50 g, 11.9 mmol) in anhydrous tetrahydrofuran (75 mL) at 0° C., was added sodium hydride (60% w/w dispersion in mineral oil, 0.72 g, 17.9 mmol). The solution was stirred at 0° C. for 0.5 h and methyl 4-(bromomethyl)benzoate (3.00 g, 13.1 mmol) was added. The solution was stirred at ambient temperature for 16 h, further sodium hydride (60% w/w dispersion in mineral oil, 0.30 g, 7.5 mmol) and methyl 4-(bromomethyl)benzoate (0.50 g, 2.2 mmol) were added and the mixture was stirred for 1 h, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 25% to 50% gradient of ethyl acetate in hexanes to afford methyl 4-[(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)methyl]benzoate (4.51 g, 86%) as a colorless solid: mp 167-169° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) δ 8.00 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.4 Hz, 2H), 7.15 (d, J=7.4 Hz, 2H), 7.03-6.96 (m, 1H), 6.73-6.68 (m, 1H), 6.48 (s, 1H), 6.22 (s, 1H), 5.10 (d, J=15.9 Hz, 1H), 4.92 (d, J=8.9 Hz, 1H), 4.84 (d, J=16.0 Hz, 1H), 4.65 (d, J=8.9 Hz, 1H), 4.19-4.04 (m, 4H), 3.87 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 177.6, 166.6, 155.3, 144.7, 141.8, 140.9, 138.4, 132.2, 130.3, 129.8, 128.9, 127.3, 124.0, 123.6, 120.9, 111.5, 109.2, 99.5, 80.1, 64.5, 63.9, 58.1, 52.2, 43.9; MS (ES+) m/z 443.9 (M+1).

Workup

  1. stirringThe solution was stirred at ambient temperature for 16 h
  2. stirringthe mixture was stirred for 1 h
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography
  6. washeluted with a 25% to 50% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-8b27b451496047ce8da211fc8a5b9311
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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