Dicyclohexylcarbodiimide → (R)-((R)-quinuclidin-3-yl) 2-(benzyloxycarbonylamino)-2-phenylacetate

HRID 1619514Notes

Reaction equation

HRID 1619514 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([OH:9])[CH2:2]2.C(=NC1CCCCC1)=NC1CCCCC1.N1(O)C2C=CC=CC=2N=N1.[CH2:35]([O:42][C:43]([NH:45][C@H:46]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:47](O)=[O:48])=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>C1COCC1>[CH2:35]([O:42][C:43]([NH:45][C@H:46]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:47]([O:9][C@@H:3]1[CH:4]2[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]2)[CH2:2]1)=[O:48])=[O:44])[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 87183(R)-(((Phenylmethoxy)carbonyl)amino)phenylacetic acidHCID 914043-Quinuclidinol, (-)-

Product 1

HCID 67605835(R)-((R)-quinuclidin-3-yl) 2-(benzyloxycarbonylamino)-2-phenylacetateYield 11.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-quinuclidin-3-ol (214 mg, 1.68 mmol), N,N′-methanediylidenedicyclohexanamine (347 mg, 1.68 mmol) and 1H-benzo[d][1,2,3]triazol-1-ol (227 mg, 1.68 mmol) were added to a solution of (R)-2-(benzyloxycarbonylamino)-2-phenylacetic acid (400 mg, 1.40 mmol) in THF (15 ml). The reaction was stirred at RT for 15 hours, and then the solvent was evaporated. DCM was added, and the insoluble solid was removed by filtration. The organic phase was washed twice with Na2CO3 and brine, dried over Na2SO4 and evaporated. The crude was purified by silica gel flash chromatography (DCM/MeOH=9/1) to obtain (R)—((R)-quinuclidin-3-yl) 2-(benzyloxycarbonylamino)-2-phenylacetate (63 mg; 11.4% yield). ((R)-quinuclidin-3-yl 2-(benzyloxycarbonylamino)-2-phenylacetate is also collected (300 mg; 54.2% yield)).

Workup

  1. customthe solvent was evaporated
  2. additionDCM was added
  3. customthe insoluble solid was removed by filtration
  4. washThe organic phase was washed twice with Na2CO3 and brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe crude was purified by silica gel flash chromatography (DCM/MeOH=9/1)

Sources & evidence

ORD record
ord-66d20d0178b140d4a00bc49bd424e004
Source dataset
uspto-grants-2014_07
Patent number
US08772314B2

Reaction notes

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