Dicyclohexylcarbodiimide → (R)-quinuclidin-3-yl 2-(benzo[b]thiophen-3-yl)-2-(methyl(phenyl)amino)acetate

HRID 469476Notes

Reaction equation

HRID 469476 reaction equation
[S:1]1[CH:5]=[C:4]([CH:6]([N:10]([CH3:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7]([OH:9])=[O:8])[C:3]2[CH:18]=[CH:19][CH:20]=[CH:21][C:2]1=2.[N:22]12[CH2:29][CH2:28][CH:25]([CH2:26][CH2:27]1)[C@@H:24](O)[CH2:23]2.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1>C1COCC1>[S:1]1[CH:5]=[C:4]([CH:6]([N:10]([CH3:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7]([O:9][C@@H:24]2[CH:25]3[CH2:28][CH2:29][N:22]([CH2:27][CH2:26]3)[CH2:23]2)=[O:8])[C:3]2[CH:18]=[CH:19][CH:20]=[CH:21][C:2]1=2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 585570282-(Benzo[b]thiophen-3-yl)-2-(methyl(phenyl)amino)acetic acid

Product 1

HCID 58556999(R)-quinuclidin-3-yl 2-(benzo[b]thiophen-3-yl)-2-(methyl(phenyl)amino)acetateYield 46.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(benzo[b]thiophen-3-yl)-2-(methyl(phenyl)amino)acetic acid (I34) (351 mg, 1.18 mmol), (R)-quinuclidin-3-ol (180 mg, 1.42 mmol), DCC (292 mg, 1.42 mmol), and HOBT (217 mg, 1.42 mmol) in dry THF (20 ml) was stirred at room temperature overnight. The solvent was evaporated, and the crude product was portioned between EtOAc and 2M K2CO3. The organic phase was washed with 2M K2CO3 and brine, dried over Na2SO4, filtered and evaporated to dryness. The crude product was purified by flash chromatography (MeCN/MeOH=8/2+0.2% NH4OH) to obtain (R)-quinuclidin-3-yl 2-(benzo[b]thiophen-3-yl)-2-(methyl(phenyl)amino)acetate (224 mg, 46.7% yield).

Workup

  1. customThe solvent was evaporated
  2. washThe organic phase was washed with 2M K2CO3 and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude product was purified by flash chromatography (MeCN/MeOH=8/2+0.2% NH4OH)

Sources & evidence

ORD record
ord-8a1dab37ab9141468435e63434c45654
Source dataset
uspto-grants-2014_01
Patent number
US08629160B2

Reaction notes

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