Pyridine → Ethyl 6-((1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentane carboxamido)spiro[2.5]oct-5-ene-5-carboxylate

HRID 2200376Notes

Reaction equation

HRID 2200376 reaction equation
[NH2:1][C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].P(Cl)(Cl)Cl.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH2:28][N:27]([C@H:30]3[CH2:34][CH2:33][C@@H:32]([C:35](O)=[O:36])[CH2:31]3)[CH2:26][CH2:25]2)=[CH:20][CH:19]=1.N1C=CC=[CH:40][CH:39]=1>C(Cl)(Cl)Cl>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([N:24]2[CH2:29][CH2:28][N:27]([C@H:30]3[CH2:34][CH2:33][C@@H:32]([C:35]([NH:1][C:2]4[CH2:7][CH2:6][C:5]5([CH2:40][CH2:39]5)[CH2:4][C:3]=4[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[O:36])[CH2:31]3)[CH2:26][CH2:25]2)=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 24387Phosphorus trichlorideHCID 312929Ethyl 2-aminocyclohex-1-ene-1-carboxylateHCID 118105560(1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentanecarboxylic acid

Product 1

HCID 118105578Ethyl 6-((1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentane carboxamido)spiro[2.5]oct-5-ene-5-carboxylateYield 38.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To an ice cold solution of ethyl 2-aminocyclohex-1-enecarboxylate (1.27 g, 6.48 mmol) in pyridine (5 ml), phosphorus trichloride (0.18 ml, 2.10 mmol) was added. After 15 min, (1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentanecarboxylic acid (0.5 g, 1.62 mmol) was added at room temperature to the mixture, followed by stirring at temperature for 6 h. Upon completion, the reaction mixture was diluted with chloroform and the organic layer was washed with saturated aqueous sodium hydrogencarbonate solution, The organic layer was separated, dried over sodium sulphate and concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography using ethyl acetate in hexane as eluent to afford ethyl 6-((1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentanecarboxamido)spiro[2.5]oct-5-ene-5-carboxylate (300 mg, 38.1%).

Workup

  1. washthe organic layer was washed with saturated aqueous sodium hydrogencarbonate solution
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue obtained
  6. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-aef74aacef91411a8e02e6dac059089e
Source dataset
uspto-grants-2016_06
Patent number
US09359367B2

Reaction notes

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