Toluene → 4-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine

HRID 1508673Notes

Reaction equation

Cl.Cl[C:3]1[N:8]=[C:7]2[CH2:9][CH2:10][CH2:11][C:6]2=[C:5]([Cl:12])[CH:4]=1.[Cl:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C([O-])([O-])=O.[K+].[K+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CCO>[Cl:12][C:5]1[CH:4]=[C:3]([C:18]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:13])[CH:19]=2)[N:8]=[C:7]2[CH2:9][CH2:10][CH2:11][C:6]=12

Participants

Conditions

Temperature: 90 °C

Procedure

An 18-mL vial was charged with 2,4-dichloro-6,7-dihydro-5H-cyclopenta[b]pyridine HCl salt (225 mg, 1 mmol, 1 eq.), (3-chlorophenyl)boronic acid (165 mg, 1.06 mmol, 1.06 eq.), tetrakis(triphenylphosphine)palladium(0) (84 mg, 0.07 mmol, 0.07 eq.), and K2CO3 (500 mg, 3.6 mmol, 3.6 eq.). Toluene (6 ml), EtOH (2 ml) and water (2.5 ml) were added. The resulting mixture was stirred under Ar at 90° C. for 4 hr. until the starting chloride was consumed. After cooling to room temperature, the aqueous layer was separated and the organic layer was concentrated on a rotary evaporator. The residue was purified by chromatography on silica gel using hexane/dichloromethane (9:1 then 8:1) as eluent to afford 4-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine, which was converted into its corresponding HCl salt by treating with 4N HCl in dioxane (228 mg, 76% yield).

Workup

customuntil the starting chloride was consumed
temperatureAfter cooling to room temperature
customthe aqueous layer was separated
concentrationthe organic layer was concentrated on a rotary evaporator
customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record: ord-99e09dc8779f49d6a779f9a66810a60b
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221843B2

Reaction notes

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