Dicyclohexylcarbodiimide → (R)-Quinuclidin-3-yl 2-amino-2-phenylacetate dihydrochloride

HRID 76976

Reaction equation

HRID 76976 reaction equation
C(OC(NC(C1C=CC=CC=1)C(O)=O)=O)(C)(C)C.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.N12CCC(CC1)[C@@H](O)C2.C(OC([NH:60][CH:61]([C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1)[C:62]([O:64][C@@H:65]1[CH:70]2[CH2:71][CH2:72][N:67]([CH2:68][CH2:69]2)[CH2:66]1)=[O:63])=O)(C)(C)C.O1CCOCC1.[ClH:85].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>C1COCC1.C(Cl)Cl>[ClH:85].[ClH:85].[NH2:60][CH:61]([C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1)[C:62]([O:64][C@@H:65]1[CH:70]2[CH2:69][CH2:68][N:67]([CH2:72][CH2:71]2)[CH2:66]1)=[O:63]

Participants

10

Reactant 7

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 5718052-(((Tert-butoxy)carbonyl)amino)-2-phenylacetic acidHCID 204431481,4-Dioxane hydrochlorideHCID 67425060(R)-quinuclidin-3-yl 2-(tert-butoxycarbonylamino)-2-phenylacetate

Product 1

HCID 67425463(R)-Quinuclidin-3-yl 2-amino-2-phenylacetate dihydrochlorideYield 97%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(tert-butoxycarbonylamino)-2-phenylacetic acid (0.90 g, 4.18 mmol), HOBt (0.68 g, 12.5 mmol), DCC (1.29 g, 6.27 mmol) and 3(R)-quinuclidinol (1.59 g, 12.5 mmol) in dry THF (50 mL) is stirred at room temperature for 16 hours (LC-MS monitoring: complete conversion). The solvent is removed under reduced pressure, the residue is taken up with EtOAc and washed twice with 2M K2CO3. The organic phase is dried over Na2SO4, filtered and evaporated to dryness. The compound is triturated with hexane to give (R)-quinuclidin-3-yl 2-(tert-butoxycarbonylamino)-2-phenylacetate as a white solid (1.46 g; 97% yield, mixture of diastereoisomers). This compound is dissolved in DCM (50 mL) and 4N HCl dioxane (5 mL) is added. The reaction is stirred at room temperature for 1 hour (LC-MS monitoring: complete conversion) and then solvent is separated. The gummy solid is triturated with hexane to give C25 as a white solid (1.26 g, 94% yield, di hydrochloride, mixture of diastereoisomers).

Workup

  1. customThe solvent is removed under reduced pressure
  2. washwashed twice with 2M K2CO3
  3. dry with materialThe organic phase is dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe compound is triturated with hexane
  7. customto give
  8. stirringThe reaction is stirred at room temperature for 1 hour (LC-MS monitoring: complete conversion)
  9. customsolvent is separated
  10. customThe gummy solid is triturated with hexane
  11. customto give C25

Sources & evidence

ORD record
ord-12d330c2c0964a97bd006600309b6d50
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Linked notes

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