Phenylacetyl chloride → [1-Bromo-6-(3-phenylacetyl-benzo[b]thiophen-2-yl)-naphthalen-2-yloxy]-acetic acid ethyl ester

HRID 1373870Notes

Reaction equation

HRID 1373870 reaction equation
[CH2:1]([O:3][C:4](=[O:27])[CH2:5][O:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:17]3[S:21][C:20]4[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=4[CH:18]=3)[CH:13]=2)[C:8]=1[Br:26])[CH3:2].[C:28]1([CH2:34][C:35](Cl)=[O:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[Sn](Cl)(Cl)(Cl)Cl>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4](=[O:27])[CH2:5][O:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:17]3[S:21][C:20]4[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=4[C:18]=3[C:35](=[O:36])[CH2:34][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:13]=2)[C:8]=1[Br:26])[CH3:2]

Participants

5

Reactant 3

HCID 7679Phenylacetyl chlorideHCID 24287Tin tetrachlorideHCID 69410849HCID 69410849, compound

Product 1

HCID 69410855[1-Bromo-6-(3-phenylacetyl-benzo[b]thiophen-2-yl)-naphthalen-2-yloxy]-acetic acid ethyl esterYield 8.9%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A mixture of (6-benzo[b]thiophen-2-yl-1-bromo-naphthalen-2-yloxy)-acetic acid ethyl ester (4.35g, 9.86 mmol), phenylacetyl chloride (4.0 mL, 30 mmol) in two portions and tin (IV) chloride (4.3 mL, 37 mmol) in chloroform (220 mL) was refluxed for five hours. It was then allowed to cool to ambient temperature and poured into ice water. It was diluted with additional chloroform and washed with water and brine. It was then dried with anhydrous magnesium sulfate, filtered and solvent evaporated. After stirring the residue in ether and filtering, the filtrate was concentrated and purified by flash chromatography using (1) 25–35% methylene chloride in hexane and 100% methylene chloride and (2) 1–8% ethyl acetate in hexane. It was then purified by HPLC using 85% acetonitrile (0.1% trifluoroacetic acid) in water as the mobile phase. Evaporating the solvent and extracting with ethyl acetate, washing with water and brine, drying with anhydrous magnesium sulfate, filtering, concentrating and drying in vacuo at 60° C. for one hour yielded [1-bromo-6-(3-phenylacetyl-benzo[b]thiophen-2-yl)-naphthalen-2-yloxy]-acetic acid ethyl ester as a yellow semi-solid (0.491 g, 8.89%); mass spectrum (+EI, [M+H]+) m/z 559/561. 1H NMR (500 MHz, DMSO-d6): δ8.28 (d, 1H, J=7.19 Hz), 8.17 (d, 1H, J=1.98 Hz), 8.12 (d, 1H, J=9.01 Hz), 8.06–8.10 (m, 1H), 7.90–7.93 (m, 1H), 7.81 (dd, 1H, J=8.78 Hz and 1.91 Hz), 7.54 (d, 1H, J=9.16 Hz), 7.45–7.50 (m, 2H), 7.13–7.19 (m, 3H), 6.91–6.94 (m, 2H), 5.13 (s, 2H), 4.19 (q, 2H, J=7.13 Hz), 3.81 (s, 2H), 1.22 ppm (t, 3H, J=7.10 Hz). Elemental Analysis for C30H23BrO4S+0.10 mol H2O: Calcd: C, 64.19; H, 4.17; N, 0.00; Found: C, 63.85; H, 4.03; N, 0.00.

Workup

  1. temperaturewas refluxed for five hours
  2. washwashed with water and brine
  3. dry with materialIt was then dried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customsolvent evaporated
  6. filtrationfiltering
  7. concentrationthe filtrate was concentrated
  8. custompurified by flash chromatography
  9. customIt was then purified by HPLC
  10. customEvaporating the solvent
  11. extractionextracting with ethyl acetate
  12. washwashing with water and brine
  13. dry with materialdrying with anhydrous magnesium sulfate
  14. filtrationfiltering
  15. concentrationconcentrating
  16. customdrying in vacuo at 60° C. for one hour

Sources & evidence

ORD record
ord-72f4cd2742bf4fdc9afad21a0674600f
Source dataset
uspto-grants-2007_01
Patent number
US07163954B2

Reaction notes

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