Ammonium Chloride → 7-chloro-4-(2-chloroethoxy)-1H-indole

HRID 962807Notes

Reaction equation

HRID 962807 reaction equation
[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[C:7]([N+:12]([O-])=O)[CH:6]=1.[CH:15]([Mg]Br)=[CH2:16].[NH4+].[Cl-]>C1COCC1>[Cl:11][C:8]1[CH:9]=[CH:10][C:5]([O:4][CH2:3][CH2:2][Cl:1])=[C:6]2[C:7]=1[NH:12][CH:16]=[CH:15]2

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 107761591-(2-Chloroethoxy)-4-chloro-3-nitrobenzeneHCID 178418507HCID 178418507, compound

Product 1

HCID 106094757-chloro-4-(2-chloroethoxy)-1H-indoleYield 158.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-(2-chloroethoxy)-4-chloro-3-nitrobenzene (10.00 g, 0.04236 mol) in THF (230 mL) stirred in a cold bath at -50° to -40° C. was added a THF solution of vinylmagnesium bromide (132 mL, 1.0M, 0.132 mol) over 2 minutes. After stirring in the cold bath for 2-2.5 hours, saturated NH4Cl (150 mL) was added to the cold solution and it was removed from the cold bath. 1M HCl was added to dissolve the precipitated solids and the mixture was stirred for 0.5 hour. The layers were separated and the aqueous phase was extracted once with diethyl ether (80 mL). The organic layer combined and dried over anhydrous magnesium sulfate, filtered and the solvent evaporated to give 15.43 g of a dark oil. Purification by chromatography (hexanesmethylene chloride, 2:1) afforded a solid which was triturated with hexane and filtered to afford the product as yellowish white solid: 3.51 g (36%); mp 73-°75 ° C.; MS El m/e 229, 231, 233 (M+);1H NMR (400 MHz, DMSO-d6) δ 3.99 (t, 2H;, J=5.1 Hz), 4.34 (t, 2H, J=5.0 Hz), 6.51 (t, 1H, J=2.7 Hz), 6.53 (d, 1H, J=7.8 Hz), 7.04 (d, 1H, J=8.0 Hz), 7.29 (t, 1H, J=2.7 Hz), 11.43 (s, 1H).

Workup

  1. customwas removed from the cold bath
  2. addition1M HCl was added
  3. dissolutionto dissolve the precipitated solids
  4. stirringthe mixture was stirred for 0.5 hour
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted once with diethyl ether (80 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customthe solvent evaporated

Sources & evidence

ORD record
ord-71fff6bd80e743afbbfe642a30029eb3
Source dataset
uspto-grants-1998_06
Patent number
US05760070

Reaction notes

Loading…