Ammonium Chloride → 2-(3-Chloropropyl)-3-methylbenzofuran

HRID 1168853Notes

Reaction equation

HRID 1168853 reaction equation
[Li]CCCC.[CH3:6][C:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[O:9][CH:8]=1.[Cl:16][CH2:17][CH2:18][CH2:19]I.[NH4+].[Cl-]>C1COCC1.[Cu]I>[Cl:16][CH2:17][CH2:18][CH2:19][C:8]1[O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:7]=1[CH3:6]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 813631-Chloro-3-iodopropaneHCID 889393-MethylbenzofuranHCID 178418339Butyllithium

Product 1

HCID 229895512-(3-Chloropropyl)-3-methylbenzofuranYield 6%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

n-BuLi in heptanes (1.5 ml, 2.4 mmol, 1.6M) was added drop wise to 3-methylbenzofuran (264 mg, 2.0 mmol) in THF (5 ml) at −20° C. under argon. The reaction mixture was stirred at −15° C. for 30 min, then 1-chloro-3-iodopropane (322 μl, 3.0 mmol) and copper (I) iodide (38 mg, 0.2 mmol) were added. The reaction was stirred at −15° C. for 1 h, then NH4Cl (sat'd aq., 5 ml) was added. The product was extracted with diethyl ether (2×30 ml) and the organic layer was washed with brine, (10 ml) dried (K2CO3), filtered and concentrated in vacuo. The product was purified by column chromatography (0-1% diethyl ether in heptanes) to give 2-(3-chloro-propyl)-3-methylbenzofuran (25 mg, 6%). 1H NMR (CDCl3): δ2.19 (tt, 2H), 2.22 (s, 3H), 2.94 (t, 2H), 3.57 (t, 2H), 7.22 (m, 2H), 7.38 (m, 1H), 7.44 (m, 1H).

Workup

  1. stirringThe reaction was stirred at −15° C. for 1 h
  2. extractionThe product was extracted with diethyl ether (2×30 ml)
  3. washthe organic layer was washed with brine, (10 ml)
  4. dry with materialdried (K2CO3)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe product was purified by column chromatography (0-1% diethyl ether in heptanes)

Sources & evidence

ORD record
ord-db928f965a23494f8a26677d09667a66
Source dataset
uspto-grants-2003_09
Patent number
US06627645B2

Reaction notes

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