Tributylphosphine → 4'-bromo-5,6-dihydro-2H-spiro[benzofuro[6,5-b]furan-3,3'-indolin]-2'-one

HRID 645157Notes

Reaction equation

HRID 645157 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([C:14]1[C:15](O)=[CH:16][C:17]3[O:21][CH2:20][CH2:19][C:18]=3[CH:22]=1)([CH2:12][OH:13])[C:5](=[O:11])[NH:6]2.C(P(CCCC)CCCC)CCC.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C(OCC)(=O)C>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([CH2:12][O:13][C:15]3[CH:16]=[C:17]4[C:18](=[CH:22][C:14]1=3)[CH2:19][CH2:20][O:21]4)[C:5](=[O:11])[NH:6]2

Participants

5

Reactant 3

HCID 13831TributylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 588724384-Bromo-3-(6-hydroxy-2,3-dihydrobenzofuran-5-yl)-3-(hydroxymethyl)indolin-2-one

Product 1

HCID 592634884'-bromo-5,6-dihydro-2H-spiro[benzofuro[6,5-b]furan-3,3'-indolin]-2'-oneYield 37.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 4-bromo-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-3-(hydroxymethyl)-1,3-dihydro-2H-indol-2-one (1.80 g, 4.80 mmol) in anhydrous ethyl acetate (50 mL) was added tributylphosphine (1.26 g, 1.54 mL, 6.24 mmol) at 0° C. under nitrogen. A solution of di-tert-butyl azodicarboxylate (1.44 g, 6.24 mmol) in anhydrous ethyl acetate (15.0 mL) was added over 10 min. The reaction solution was stirred for 2 h, and then quenched with saturated ammonium chloride solution (30.0 mL). After the aqueous layer was separated, the organic layer was washed with 10% aqueous HCl solution (2×25.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography eluting with ethyl acetate-hexane (70%) to obtain a solid which was triturated with diethyl ether to give the title compound (0.64 g, 37%) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) δ 10.77 (s, 1H), 7.18-7.13 (m, 1H), 7.08 (d, 1H), 6.90 (d, 1H), 6.47 (s, 1H), 6.30 (s, 1H), 4.80 (ABq, 2H), 4.46 (t, 2H), 2.92 (t, 2H); 13C NMR (75 MHz, DMSO-d6) δ 178.7, 162.2, 161.7, 144.5, 131.1, 131.0, 126.1, 119.8, 119.2, 119.1, 118.3, 109.7, 92.4, 77.6, 72.5, 59.2, 28.8; MS (ES−) m/z 358.4 (M−1), 356.3 (M−1).

Workup

  1. customquenched with saturated ammonium chloride solution (30.0 mL)
  2. customAfter the aqueous layer was separated
  3. washthe organic layer was washed with 10% aqueous HCl solution (2×25.0 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo to dryness
  7. washeluting with ethyl acetate-hexane (70%)
  8. customto obtain a solid which
  9. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-3f0d7b95d446469287823a8cbc501eb2
Source dataset
uspto-grants-2010_04
Patent number
US07700641B2

Reaction notes

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