Dicyclohexylcarbodiimide → (R)-quinuclidin-3-yl 2-(4-fluorophenylamino)-2-phenylacetate

HRID 1044058Notes

Reaction equation

HRID 1044058 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:11]([OH:13])=[O:12])=[CH:5][CH:4]=1.[N:20]12[CH2:27][CH2:26][CH:23]([CH2:24][CH2:25]1)[C@@H:22](O)[CH2:21]2.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[F:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:11]([O:13][C@@H:22]2[CH:23]3[CH2:26][CH2:27][N:20]([CH2:25][CH2:24]3)[CH2:21]2)=[O:12])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 10868Dicyclohexylcarbodiimide2×HCID 757711-Hydroxybenzotriazole2×HCID 914043-Quinuclidinol, (-)-2×HCID 671248462-(4-Fluorophenylamino)-2-phenylacetic acid hydrochloride

Product 1

HCID 58556923(R)-quinuclidin-3-yl 2-(4-fluorophenylamino)-2-phenylacetateYield 38.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(4-Fluorophenylamino)-2-phenylacetic acid hydrochloride (I38) (2.00 g, 8.15 mmol) was dissolved in THF (25 ml), and (R)-quinuclidin-3-ol (1.14 g, 8.97 mmol) was added. To the resulting solution, HOBt (1.10 g, 8.15 mmol) and DCC (0.841 g, 4.08 mmol) were added, and the mixture was stirred at room temperature for three days. Then a second portion of HOBt (0.55 g, 4.08 mmol), DCC (0.84 g, 4.08 mmol) and (R)-quinuclidin-3-ol (0.52 g, 4.08 mmol) were added, and the mixture was stirred at room temperature overnight. THF was removed under vacuum, and the residue was treated with H2O and extracted twice with EtOAc. The combined organic phases were washed with saturated Na2CO3 and dried over Na2SO4, filtered and the solvent was evaporated in vacuo. The crude was purified by flash chromatography (EtOAc/MeOH=9/1 to 75/25) to afford (R)-quinuclidin-3-yl 2-(4-fluorophenylamino)-2-phenylacetate (1.1 g, 3.10 mmol, 38.1% yield, mixture of diasteromers).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. customTHF was removed under vacuum
  3. additionthe residue was treated with H2O
  4. extractionextracted twice with EtOAc
  5. washThe combined organic phases were washed with saturated Na2CO3
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was evaporated in vacuo
  9. customThe crude was purified by flash chromatography (EtOAc/MeOH=9/1 to 75/25)

Sources & evidence

ORD record
ord-743082295f3440a688a5b25b2b4e98ff
Source dataset
uspto-grants-2013_10
Patent number
US08563577B2

Reaction notes

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