Monobenzone → 3-[5-(benzyloxy)-2-hydroxyphenyl]-1-[(5-chloro-2-thienyl)methyl]-3-hydroxy-1,3-dihydro-2H-indol-2-one

HRID 1407448Notes

Reaction equation

HRID 1407448 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.[Cl:21][C:22]1[S:26][C:25]([CH2:27][N:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:30](=[O:37])[C:29]2=[O:38])=[CH:24][CH:23]=1>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([OH:15])=[C:13]([C:30]2([OH:37])[C:31]3[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=3)[N:28]([CH2:27][C:25]3[S:26][C:22]([Cl:21])=[CH:23][CH:24]=3)[C:29]2=[O:38])[CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7638MonobenzoneHCID 220224391-(5-Chloro-thiophen-2-yl-methyl)-1h-indole-2,3-dioneHCID 178418918HCID 178418918, compound

Product 1

HCID 673570873-[5-(benzyloxy)-2-hydroxyphenyl]-1-[(5-chloro-2-thienyl)methyl]-3-hydroxy-1,3-dihydro-2H-indol-2-oneYield 34.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a pale yellow solution of 4-(benzyloxy)phenol (9.01 g, 45.0 mmol) in anhydrous tetrahydrofuran (100.0 mL) was added isopropylmagnesium chloride (26.3 mL, 52.5 mmol, 2.0 M solution in tetrahydrofuran) at 0° C. The reaction solution was stirred for 0.5 h followed by the addition of 1-((5-chlorothiophen-2-yl)methyl)indoline-2,3-dione (8.31 g, 30.0 mmol) in portions. The reaction mixture was stirred for 16 h at ambient temperature. The reaction was quenched by the addition of saturated ammonium chloride solution (50.0 mL) and concentrated in vacuo to dryness. The residue was diluted with ethyl acetate (100 mL), washed with saturated ammonium chloride solution (2×25.0 mL), brine (2×25 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was purified by column chromatography with ethyl acetate to afford 3-[5-(benzyloxy)-2-hydroxyphenyl]-1-[(5-chlorothiophen-2-yl)methyl]-3-hydroxy-1,3-dihydro-2H-indol-2-one (4.90 g, 28%) as a colourless solid: mp 174-175° C.; 1H NMR (300 MHz, CDCl3) δ8.45 (br, 1H), 7.40-7.27 (m, 7H), 7.14 (dd, J=7.5, 7.5 Hz, 1H), 6.92 (d, J=2.9 Hz, 1H), 6.89 (s, 1H), 6.83 (d, J=2.9 Hz, 1H), 6.79 (d, J=3.7 Hz, 1H), 6.70 (d, J=3.7 Hz, 1H), 6.43 (d, J=2.9 Hz, 1H), 4.86 (ABq, 2H), 4.84 (s, 2H); 13C NMR (75 MHz, CDCl3) δ178.3, 152.6, 149.790, 141.7, 136.8, 135.8, 130.4, 130.1, 129.1, 128.6, 127.9, 127.6, 126.3, 126.2, 126.0, 125.9, 124.3, 120.2, 116.3, 114.4, 109.6, 79.1, 70.6, 39.2; MS (ES+) m/z 478.2 (M−1), 476.2 (M−1).

Workup

  1. stirringThe reaction mixture was stirred for 16 h at ambient temperature
  2. customThe reaction was quenched by the addition of saturated ammonium chloride solution (50.0 mL)
  3. concentrationconcentrated in vacuo to dryness
  4. additionThe residue was diluted with ethyl acetate (100 mL)
  5. washwashed with saturated ammonium chloride solution (2×25.0 mL), brine (2×25 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo to dryness
  9. customThe residue was purified by column chromatography with ethyl acetate

Sources & evidence

ORD record
ord-7a68adb4363d455f825bfc724dc496f1
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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