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

HRID 469479Notes

Reaction equation

HRID 469479 reaction equation
[S:1]1[CH:5]=[C:4]([CH:6]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=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]([NH:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=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 585569862-(Benzo[b]thiophen-3-yl)-2-(benzylamino)acetic acid

Product 1

HCID 58557025(R)-quinuclidin-3-yl 2-(benzo[b]thiophen-3-yl)-2-(benzylamino)acetateYield 12.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(benzo[b]thiophen-3-yl)-2-(benzylamino)acetic acid (I37) (303 mg, 1.02 mmol), (R)-quinuclidin-3-ol (156 mg, 1.22 mmol), DCC (252 mg, 1.22 mmol), and HOBT (187 mg, 1.22 mmol) in dry THF (20 ml) was stirred at room temperature overnight. The solvent was evaporated, and the crude product was partitioned 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 (CH3CN/MeOH=8/2+0.2% NH4OH) to obtain (R)-quinuclidin-3-yl 2-(benzo[b]thiophen-3-yl)-2-(benzylamino)acetate (53 mg, 12.8% yield).

Workup

  1. customThe solvent was evaporated
  2. customthe crude product was partitioned between EtOAc and 2M K2CO3
  3. washThe organic phase was washed with 2M K2CO3 and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe crude product was purified by flash chromatography (CH3CN/MeOH=8/2+0.2% NH4OH)

Sources & evidence

ORD record
ord-58919b11362448ba9ddd1eb45536928a
Source dataset
uspto-grants-2014_01
Patent number
US08629160B2

Reaction notes

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