Oxalyl chloride → 2-(6-chloro-1H-indol-3-yl)-2-oxoacetyl chloride

HRID 1936616Notes

Reaction equation

HRID 1936616 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[C:11](Cl)(=[O:15])[C:12]([Cl:14])=[O:13]>C(OCC)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:15])[C:12]([Cl:14])=[O:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 65578Oxalyl chlorideHCID 871116-Chloroindole

Product 1

HCID 106816002-(6-chloro-1H-indol-3-yl)-2-oxoacetyl chloride

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

A solution of 6-chloro-1H-indole (15 g) in diethyl ether (300 mL) was cooled to 0° C. and treated with a solution of oxalyl chloride (9.4 mL) in diethyl ether (30 mL). The mixture was stirred for 16 hours at room temperature. Filtration gave 2-(6-chloro-1H-indol-3-yl)-2-oxoacetyl chloride as a crystalline material (15.5 g). A part of this product (2.5 g) was dissolved in dry tetrahydrofuran (25 mL) and added dropwise to a solution of 1-(1H-indol-4-yl)piperazine (1.4 g) and triethylamine (15 mL) in tetrahydrofuran (100 mL). After stirring for 16 hours the reaction mixture was concentrated in vacuo. The remaining oil was purified by flash chromatography (eluent: ethyl acetate/methanol/triethylamine 85:10:5) giving 1-(2-(6-chloro-1H-indol-3-yl)-1,2-dioxoethyl)-4-(1H-indol-4-yl)piperazine (1.6 g) as a crystalline material. This product was suspended in tetrahydrofuran (25 mL) and added dropwise to a suspension of lithium aluminium hydride (1.5 g) in tetrahydrofuran (50 mL). The mixture was refluxed for 4 hours and cooled to 0° C. followed by subsequent addition of water (3 mL), 15% aq. sodium hydroxide (1.5 mL), and water (7.5 mL). Filtration and standard work-up gave a yellow oil which was converted to the title oxalate salt (1.5 g) from an acetone solution by addition of oxalic acid. Mp 229-31° C. 1H NMR (DMSO-d6): 3.10 (t, 2H); 3.25-3.55 (m, 10H); 6.45 (s, 1H); 6.50 (d, 1H); 6.90-7.10 (m, 3H); 7.25-7.35 (m, 2H); 7.45 (s, 1H); 7.65 (d, 1H); 11.12 (s, 2H), MS m/z (%): 379 (MH+, 18%), 214 (16%), 199 (17%), 178 (16%), 143 (13%).

Workup

  1. filtrationFiltration

Sources & evidence

ORD record
ord-bb6480f95dd8434d9bbe4e2242f2ed4e
Source dataset
uspto-grants-2002_05
Patent number
US06391882B1

Reaction notes

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