Tin tetrachloride → [1-Bromo-6-(3-pentanoyl-benzo[b]thiophen-2-yl)-naphthalen-2-yloxy]-acetic acid ethyl ester

HRID 1373866Notes

Reaction equation

HRID 1373866 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](Cl)(=[O:33])[CH2:29][CH2:30][CH2:31][CH3:32].[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:28](=[O:33])[CH2:29][CH2:30][CH2:31][CH3:32])[CH:13]=2)[C:8]=1[Br:26])[CH3:2]

Participants

5

Reactant 3

HCID 24287Tin tetrachloride2×HCID 61186Valeryl chloride2×HCID 69410849HCID 69410849, compound

Product 1

HCID 69411771[1-Bromo-6-(3-pentanoyl-benzo[b]thiophen-2-yl)-naphthalen-2-yloxy]-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a 0° C. solution of (6-benzo[b]thiophen-2-yl-1-bromo-naphthalen-2-yloxy)-acetic acid ethyl ester (3.0 g, 6.8 mmol) in chloroform (90 mL) was added valeryl chloride (0.97 mL, 8.2 mmol) and tin (IV) chloride (1.2 mL, 10 mmol). This reaction mixture was allowed to stir at ambient temperature for three hours. It was then refluxed for a total of 17.5 hours. During refluxing was added valeryl chloride (1.94 mL, 16.4 mmol) in two portions and tin (IV) chloride (2.4 mL, 20 mmol) in two portions. The reaction mixture was allowed to cool to ambient temperature. It was then poured into ice water and diluted with additional chloroform. The organic phase was washed with water and brine. It was then dried with anhydrous magnesium sulfate, filtered, and solvent evaporated. The residue was then purified several times by flash chromatography using (1) 20%–50% methylene chloride in hexane and 100% methylene chloride, (2) 100% hexane, 1–10% ethyl acetate in hexane and (3) 100% hexane and 5–40% 1,2-dichloroethane in hexane and 100% methylene chloride. Further purification was done by IPLC using 90% acetonitrile (0.1% formic acid) in water as the mobile system. 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 30 minutes yielded [1-bromo-6-(3-pentanoyl-benzo[b]thiophen-2-yl)-naphthalen-2-yloxy]-acetic acid ethyl ester as a clear, light brown gum (0.0979 g, 2.72%); 1H NMR (400 MHz, DMSO-d6): δ8.23 (d, 1H, J=8.81 Hz), 8.06–8.14 (m, 3H), 7.94–7.96 (m, 1H), 7.72 (dd, 1H, J=8.81 Hz and 1.79 Hz), 7.44–7.52 (m, 3H), 5.11 (s, 2H), 4.19 (q, 2H, J=7.11 Hz), 2.37 (t, 2H, J=7.30 Hz), 1.18–1.20 (m, 2H), 1.38–1.45 (m, 2H), 0.9–1.05 (m, 3H), 0.56 ppm (t, 3H, J=7.37 Hz).

Workup

  1. temperatureIt was then refluxed for a total of 17.5 hours
  2. temperatureDuring refluxing
  3. temperatureto cool to ambient temperature
  4. washThe organic phase was washed with water and brine
  5. dry with materialIt was then dried with anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customsolvent evaporated
  8. customThe residue was then purified several times by flash chromatography
  9. customFurther purification
  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 30 minutes

Sources & evidence

ORD record
ord-a4f33b20e10b443fae956a15b9eccc12
Source dataset
uspto-grants-2007_01
Patent number
US07163954B2

Reaction notes

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