Dicyclohexylcarbodiimide → (R)-quinuclidin-3-yl 2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetate

HRID 469470Notes

Reaction equation

HRID 469470 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([CH:10]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:11]([OH:13])=[O:12])[C:2]1=2.[N:21]12[CH2:28][CH2:27][CH:24]([CH2:25][CH2:26]1)[C@@H:23](O)[CH2:22]2.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1>C1COCC1>[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([CH:10]([NH:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:11]([O:13][C@@H:23]3[CH:24]4[CH2:27][CH2:28][N:21]([CH2:26][CH2:25]4)[CH2:22]3)=[O:12])[C:2]1=2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 585570382-(Benzo[b]thiophen-7-yl)-2-(phenylamino)acetic acid

Product 1

HCID 58557003(R)-quinuclidin-3-yl 2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetateYield 42.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetic acid (I26) (303 mg, 1.07 mmol), (R)-quinuclidin-3-ol (136 mg, 1.07 mmol), DCC (221 mg, 1.07 mmol) and HOBT (164 mg, 1.07 mmol) in THF (20 ml) was stirred at r.t. for three days. THF was evaporated, and the crude product was taken up with EtOAc and washed twice with 2M K2CO3, and then with brine. The organic phase was dried over Na2SO4, filtered and evaporated to dryness. The crude was purified by flash chromatography (EtOAc/MeOH=9/1 to EtOAc/MeOH=9/1+0.5% NH4OH) to obtain (R)-quinuclidin-3-yl 2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetate (180 mg, 42.9% yield).

Workup

  1. customTHF was evaporated
  2. washwashed twice with 2M K2CO3
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude was purified by flash chromatography (EtOAc/MeOH=9/1 to EtOAc/MeOH=9/1+0.5% NH4OH)

Sources & evidence

ORD record
ord-fdb1ceb0205f43978a4758de33e9a484
Source dataset
uspto-grants-2014_01
Patent number
US08629160B2

Reaction notes

Loading…