Tributylphosphine → 1'-{[2,5-dimethyl-1-(1-methylethyl)-1H-pyrrol-3-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

HRID 2385142Notes

Reaction equation

HRID 2385142 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:21].[CH:22]([N:25]1[C:29]([CH3:30])=[CH:28][C:27]([CH2:31]O)=[C:26]1[CH3:33])([CH3:24])[CH3:23].C(P(CCCC)CCCC)CCC.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:33][C:26]1[N:25]([CH:22]([CH3:24])[CH3:23])[C:29]([CH3:30])=[CH:28][C:27]=1[CH2:31][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:21]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 17604272(1-isopropyl-2,5-dimethyl-1H-pyrrol-3-yl)methanolHCID 53375495spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

Product 1

HCID 593522821'-{[2,5-dimethyl-1-(1-methylethyl)-1H-pyrrol-3-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-oneYield 24.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.84 g, 3.0 mmol) and (1-isopropyl-2,5-dimethyl-1H-pyrrol-3-yl)methanol (0.50 g, 3.0 mmol) in anhydrous tetrahydrofuran (15 mL) was added dropwise tributylphosphine (0.90 g, 1.5 mmol). The solution was cooled to 0° C. and diethyl azodicarboxylate (0.78 g, 4.5 mmol) was added. The solution was stirred at ambient temperature for 16 h then quenched with saturated ammonium chloride (50 mL). The aqueous solution was extracted with ethyl acetate (200 mL), dried on magnesium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by flash chromatography with ethyl acetate in hexanes (15% to 50% gradient) to afford 1′-{[2,5-dimethyl-1-(1-methylethyl)-1H-pyrrol-3-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.32 g, 24%) as a colorless solid: mp 169-171° C.; 1H NMR (300 MHz, CDCl3) δ 7.27-7.20 (m, 1H), 7.11 (d, J=7.5 Hz, 1H), 7.02-6.95 (m, 2H), 6.49 (s, 1H), 6.09 (s, 1H), 5.85-5.82 (m, 2H), 5.77 (br s, 1H), 4.77 (ABq, 2H), 4.69 (ABq, 2H), 4.37 (sep, J=7.0 Hz, 1H), 2.33 (s, 3H), 2.22 (s, 3H), 1.43 (d, J=7.0 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ194.7, 177.2, 155.9, 148.7, 142.9, 142.2, 132.5, 128.7, 127.0, 125.5, 123.6, 122.9, 119.9, 113.0, 109.6, 107.6, 103.2, 101.4, 93.5, 80.5, 58.2, 47.3, 37.0, 22.2, 14.1, 11.5; MS (ES+) m/z 431.20 (M+1).

Workup

  1. customthen quenched with saturated ammonium chloride (50 mL)
  2. extractionThe aqueous solution was extracted with ethyl acetate (200 mL)
  3. customdried on magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo to dryness
  6. customThe residue was purified by flash chromatography with ethyl acetate in hexanes (15% to 50% gradient)

Sources & evidence

ORD record
ord-eea94984aa104caf83b9991f9d09b09e
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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