Dicyclohexylcarbodiimide → (R)-quinuclidin-3-yl 2-(4-methyl-3-oxopiperazin-1-yl)-2-phenylacetate

HRID 404643Notes

Reaction equation

HRID 404643 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]([OH:11])=[O:10])[CH2:4][C:3]1=[O:18].C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[N:44]12[CH2:51][CH2:50][CH:47]([CH2:48][CH2:49]1)[C@@H:46](O)[CH2:45]2>C1COCC1>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]([O:11][C@@H:46]2[CH:47]3[CH2:50][CH2:51][N:44]([CH2:49][CH2:48]3)[CH2:45]2)=[O:10])[CH2:4][C:3]1=[O:18]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 584907532-(4-Methyl-3-oxopiperazin-1-yl)-2-phenylacetic acid

Product 1

HCID 86688902(R)-quinuclidin-3-yl 2-(4-methyl-3-oxopiperazin-1-yl)-2-phenylacetateYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(4-Methyl-3-oxopiperazin-1-yl)-2-phenylacetic acid (170 mg, 0.68 mmol) was suspended in dry THF (6 ml) and DCC (283 mg, 1.37 mmol), HOBT (185 mg, 1.37 mmol) and (R)-quinuclidin-3-ol (174 mg, 1.37 mmol) were sequentially added. The reaction was stirred at room temperature for two days and then the insoluble was filtered off. The solution was evaporated and the residue was purified by flash chromatography (DCM/MeOH/NH4OH=96/4/0.4) to obtain (R)-quinuclidin-3-yl 2-(4-methyl-3-oxopiperazin-1-yl)-2-phenylacetate (175 mg, 54.1% yield over 2 steps) as a off-white spongy solid

Workup

  1. filtrationthe insoluble was filtered off
  2. customThe solution was evaporated
  3. customthe residue was purified by flash chromatography (DCM/MeOH/NH4OH=96/4/0.4)

Sources & evidence

ORD record
ord-c118ea923fe34065b1a503a0f282f517
Source dataset
uspto-grants-2014_06
Patent number
US08748613B2

Reaction notes

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