2-Chlorobenzyl chloride → 7-Chloro-2-ethyl-1H-indene

HRID 1421451Notes

Reaction equation

HRID 1421451 reaction equation
C([O-])(=O)CCC.[Na+].C([N-]C(C)C)(C)C.[Li+].[CH3:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].C1COCC1.C(C1C=CC=CC=1)C.[Cl:36][C:37]1[CH:44]=CC=C[C:38]=1[CH2:39]Cl.O=S(Cl)Cl>C1COCC1>[CH2:17]([C:18]1[CH2:39][C:38]2[C:20]([CH:19]=1)=[CH:21][CH:22]=[CH:44][C:37]=2[Cl:36])[CH3:16]

Participants

7

Reactant 5

HCID 119062-Chlorobenzyl chlorideHCID 24386Thionyl ChlorideHCID 2724682Lithium diisopropylamideHCID 5222465Sodium ButyrateHCID 22742125Tetrahydrofuran heptane ethylbenzol

Product 1

HCID 121494117-Chloro-2-ethyl-1H-indene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 12L round-bottom flask was equipped with a mechanical stirrer, thermometer and reflux condenser. 385 g sodium butanoate (3.5 mol) and 2L THF were added to form a slurry. 2.625L lithium diisopropylamide, 2M in heptane/THF/ethyl-benzene (5.25 mol, 50% excess) were added at ambient temperature, and then stirred for 24 hours. Then 705 g 2-chlorobenzyl chloride (4.375 mol, 25% excess) was added, and the reaction stirred for another 24 hours. Once completed, the reaction was quenched by adding 1500 mL H2O, and the solution allowed to separate. The aqueous layer, pH=13, was separated and neutralized by addition of 12N HCl to obtain pH=7.0, at which point a phase separation occurs. 2-(2-chlorobenzyl) butanoic acid was concentrated in the organic layer. Synthesis of 2-ethyl-7-chloroindene was completed by the same sequence of reactions and method as described in Example 1, beginning with the addition of SOCl2. See FIGS. 1 and 3. The product, 2-ethyl-7-chloroindene, was obtained by distillation at 110-114° C. under 1-3 mm Hg. Yield was 205 g (33% overall) of a clear, colorless oil.

Workup

  1. temperaturethermometer and reflux condenser
  2. customto form a slurry
  3. stirringthe reaction stirred for another 24 hours
  4. customthe reaction was quenched
  5. additionby adding 1500 mL H2O
  6. customto separate
  7. customThe aqueous layer, pH=13, was separated
  8. additionneutralized by addition of 12N HCl
  9. customto obtain pH=7.0
  10. customat which point a phase separation
  11. concentration2-(2-chlorobenzyl) butanoic acid was concentrated in the organic layer
  12. customSynthesis of 2-ethyl-7-chloroindene

Sources & evidence

ORD record
ord-b967999830164282ad27a580c0e344c2
Source dataset
uspto-grants-2000_06
Patent number
US06075171

Reaction notes

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