Dicyclohexylcarbodiimide → ethyl 3-(1-(6-methoxypyridin-3-yl)-2-oxo-2-((R)-quinuclidin-3-yloxy)ethylamino)benzoate

HRID 469497Notes

Reaction equation

HRID 469497 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([NH:12][CH:13]([C:17]2[CH:18]=[N:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=2)[C:14]([OH:16])=[O:15])[CH:9]=[CH:10][CH:11]=1)=[O:5])[CH3:2].[N:25]12[CH2:32][CH2:31][CH:28]([CH2:29][CH2:30]1)[C@@H:27](O)[CH2:26]2.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[CH3:24][O:23][C:20]1[N:19]=[CH:18][C:17]([CH:13]([NH:12][C:8]2[CH:7]=[C:6]([CH:11]=[CH:10][CH:9]=2)[C:4]([O:3][CH2:1][CH3:2])=[O:5])[C:14](=[O:16])[O:15][C@@H:27]2[CH:28]3[CH2:31][CH2:32][N:25]([CH2:30][CH2:29]3)[CH2:26]2)=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 585569882-(3-(Ethoxycarbonyl)phenylamino)-2-(6-methoxypyridin-3-yl)acetic acid

Product 1

HCID 58556990ethyl 3-(1-(6-methoxypyridin-3-yl)-2-oxo-2-((R)-quinuclidin-3-yloxy)ethylamino)benzoateYield 31.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(3-(ethoxycarbonyl)phenylamino)-2-(6-methoxypyridin-3-yl)acetic acid (I64) (951 mg, 2.51 mmol), (R)-quinuclidin-3-ol (694 mg, 5.47 mmol), HOBT (837 mg, 5.47 mmol), and DCC (1.13 g, 5.47 mmol) in dry THF (35 ml) was stirred at room temperature overnight. The solvent was evaporated, and the crude product was partitioned between DCM and 2M K2CO3. The organic phase was dried over Na2SO4, filtered and evaporated to dryness. The crude product was purified by flash chromatography (DMC/MeOH=97/3 to 95/5) to obtain ethyl 3-(1-(6-methoxypyridin-3-yl)-2-oxo-2-((R)-quinuclidin-3-yloxy)ethylamino)benzoate (348 mg, 27.5% yield).

Workup

  1. customThe solvent was evaporated
  2. customthe crude product was partitioned between DCM and 2M K2CO3
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude product was purified by flash chromatography (DMC/MeOH=97/3 to 95/5)

Sources & evidence

ORD record
ord-0948b06e0d1748c99a0634691150f52c
Source dataset
uspto-grants-2014_01
Patent number
US08629160B2

Reaction notes

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