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

HRID 469481Notes

Reaction equation

HRID 469481 reaction equation
[S:1]1[CH:5]=[C:4]([CH:6]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[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.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[S:1]1[CH:5]=[C:4]([CH:6]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[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 585569922-(Benzo[b]thiophen-3-yl)-2-(3-fluorophenylamino)acetic acid

Product 1

HCID 58556987(R)-quinuclidin-3-yl 2-(benzo[b]thiophen-3-yl)-2-(3-fluorophenylamino)acetateYield 45.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(benzo[b]thiophen-3-yl)-2-(3-fluorophenylamino)acetic acid (I40) (677 mg, 2.25 mmol), (R)-quinuclidin-3-ol (343 mg, 2.70 mmol), HOBT (413 mg, 2.70 mmol), and DCC (556 mg, 2.70 mmol) in THF (20 ml) was stirred at room temperature overnight. THF was evaporated, and the crude product was partitioned between EtOAc and 1M K2CO3. The organic phase was dried over Na2SO4, filtered and evaporated to dryness. The crude product was purified by flash chromatography (DCM/MeOH=98/2 to 95/5) to obtain (R)-quinuclidin-3-yl 2-(benzo[b]thiophen-3-yl)-2-(3-fluorophenylamino)acetate (421 mg, 45.6% yield over two steps).

Workup

  1. customTHF was evaporated
  2. customthe crude product was partitioned between EtOAc and 1M 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 (DCM/MeOH=98/2 to 95/5)

Sources & evidence

ORD record
ord-6dabe47da4814fea8907b15b5a86e5f0
Source dataset
uspto-grants-2014_01
Patent number
US08629160B2

Reaction notes

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