Tributylphosphine → 7'-bromospiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

HRID 2385144Notes

Reaction equation

HRID 2385144 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8](=[O:11])[C:7]2([C:14]1[C:22](O)=[CH:21][C:17]2[O:18][CH2:19][O:20][C:16]=2[CH:15]=1)[CH2:12][OH:13].C(P(CCCC)CCCC)CCC.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8](=[O:11])[C:7]12[C:14]2=[CH:15][C:16]3[O:20][CH2:19][O:18][C:17]=3[CH:21]=[C:22]2[O:13][CH2:12]1

Participants

5

Reactant 3

HCID 13831TributylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 685969097-bromo-3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-1,3-dihydro-2H-indol-2-one

Product 1

HCID 593525017'-bromospiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-oneYield 53.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspended mixture of 7-bromo-3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-1,3-dihydro-2H-indol-2-one (4.70 g, 12.4 mmol) in anhydrous tetrahydrofuran (120 mL) was added tributylphosphine (3.8 mL, 15.5 mmol), followed by additional of di-tert-butyl azodicarboxylate (3.58 g, 15.5 mmol) in anhydrous tetrahydrofuran (25 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 h and at ambient temperature for 16 h. The reaction was quenched by addition of saturated aqueous ammonium chloride solution (150 mL) and extracted with ethyl acetate (3×200 mL). The combined organic solution was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by column chromatography with ethyl acetate in hexanes (10% to 30% gradient) to give 7′-bromospiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (2.4 g, 53%) as a colorless solid: mp 240° C. (dec.); 1H NMR (300 MHz, DMSO-d6) δ10.88 (s, 1H), 7.34 (dd, J=8.1, 1.0 Hz, 1H), 7.10 (d, J=7.2 Hz, 1H), 6.93 (dd, J=8.1, 7.5 Hz, 1H), 6.68 (s, 1H), 6.36 (s, 1H), 5.93 (dd, J=2.9, 0.8 Hz, 2H), 4.77 (d, J=9.4 Hz, 1H), 4.65 (d, J=9.4 Hz, 1H); 13C NMR (75 MHz, DMSO-d6) δ 178.1, 155.3, 148.2, 141.6, 141.1, 134.2, 131.4, 123.8, 122.8, 119.4, 103.1, 102.0, 101.3, 93.1, 79.9, 58.8; MS (ES+) m/z 360.2 (M+1), 362.2 (M+1); MS (ES−) m/z 358.2 (M−1), 360.2 (M−1).

Workup

  1. customat 0° C
  2. customThe reaction was quenched by addition of saturated aqueous ammonium chloride solution (150 mL)
  3. extractionextracted with ethyl acetate (3×200 mL)
  4. washThe combined organic solution was washed with brine (100 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to dryness
  8. customThe residue was purified by column chromatography with ethyl acetate in hexanes (10% to 30% gradient)

Sources & evidence

ORD record
ord-4d8adf1f45924b11afa8069e3688a3b4
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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