Lithium Hydroxide → 6-((1S,3S)-3-(4-(4-chlorophenyl) piperazin-1-yl)cyclopentanecarboxamido)spiro[2.5]oct-5-ene-5-carboxylic acid

HRID 2200377Notes

Reaction equation

HRID 2200377 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C@H:14]3[CH2:18][CH2:17][C@@H:16]([C:19]([NH:21][C:22]4[CH2:29][CH2:28][C:25]5([CH2:27][CH2:26]5)[CH2:24][C:23]=4[C:30]([O:32]CC)=[O:31])=[O:20])[CH2:15]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[OH-].[Li+]>CO.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:9][CH2:10][N:11]([C@H:14]3[CH2:18][CH2:17][C@@H:16]([C:19]([NH:21][C:22]4[CH2:29][CH2:28][C:25]5([CH2:27][CH2:26]5)[CH2:24][C:23]=4[C:30]([OH:32])=[O:31])=[O:20])[CH2:15]3)[CH2:12][CH2:13]2)=[CH:4][CH:3]=1.[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:9][CH2:10][N:11]([C@H:14]3[CH2:18][CH2:17][C@H:16]([C:19]([NH:21][C:22]4[CH2:29][CH2:28][C:25]5([CH2:27][CH2:26]5)[CH2:24][C:23]=4[C:30]([OH:32])=[O:31])=[O:20])[CH2:15]3)[CH2:12][CH2:13]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 118105578Ethyl 6-((1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentane carboxamido)spiro[2.5]oct-5-ene-5-carboxylate

Product 2

HCID 1181055656-((1S,3S)-3-(4-(4-chlorophenyl) piperazin-1-yl)cyclopentanecarboxamido)spiro[2.5]oct-5-ene-5-carboxylic acidHCID 1181055916-((1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentane carboxamido)spiro[2.5]oct-5-ene-5-carboxylic acid

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

Ethyl 6-((1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentane carboxamido)spiro[2.5]oct-5-ene-5-carboxylate (0.3 g, 0.62 mmol) was dissolved in 10 ml of tetrahudrofuran/methanol/water (3:1:1). To this solution was added lithium hydroxide (0.12 g, 2.8 mmol). The mixture was stirred at room temperature overnight, concentrated, and acidified using 1 N hydrochloric acid to pH 6. To the resulting white slurry was added water (20 ml). The mixture was extracted with dichloromethane (2×50 ml). The organic layer was dried over sodium sulfate and concentrated to afford the title compound 6-((1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentane carboxamido)spiro[2.5]oct-5-ene-5-carboxylic acid along with its corresponding diastereomer 6-((1S,3S)-3-(4-(4-chlorophenyl) piperazin-1-yl)cyclopentanecarboxamido)spiro[2.5]oct-5-ene-5-carboxylic acid as observed on the HPLC column.

Workup

  1. concentrationconcentrated
  2. additionTo the resulting white slurry was added water (20 ml)
  3. extractionThe mixture was extracted with dichloromethane (2×50 ml)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-64250faea3514e658325149420730005
Source dataset
uspto-grants-2016_06
Patent number
US09359367B2

Reaction notes

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