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

HRID 1255011Notes

Reaction equation

HRID 1255011 reaction equation
[CH2:1]([NH:8][CH:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[N:44]12[CH2:51][CH2:50][CH:47]([CH2:48][CH2:49]1)[C@@H:46](O)[CH2:45]2>C1COCC1>[CH2:1]([NH:8][CH:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10]([O:12][C@@H:46]1[CH:47]2[CH2:50][CH2:51][N:44]([CH2:49][CH2:48]2)[CH2:45]1)=[O:11])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 2826470(Benzylamino)Phenylacetic Acid

Product 1

HCID 46840418(R)-quinuclidin-3-yl 2-(benzylamino)-2-phenylacetateYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(benzylamino)-2-phenylacetic acid (I23) (0.94 g, 3.90 mmol), DCC (0.97 g, 4.70 mmol), HOBt (0.63 g, 4.07 mmol) and 3(R)-quinuclidinol (1.51 g, 11.7 mmol) in dry THF (30 mL) is stirred at room temperature overnight under nitrogen flowstream (LC-MS monitoring: complete conversion). The solvent is evaporated and the residue is taken up with EtOAc and washed twice with water. The organic phase is dried over Na2SO4, filtered and evaporated to dryness. The resulting crude is purified by flash chromatography (DCM/MeOH=98/2, 0.2% NH3(aq.) to 95/5, 0.5% NH3(aq.)) to give a mixture of diastereoisomers 1 and 2 of C24 (231 mg, 52% yield, mixture of diasteroisomers).

Workup

  1. customThe solvent is evaporated
  2. washwashed twice with water
  3. dry with materialThe organic phase is dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe resulting crude is purified by flash chromatography (DCM/MeOH=98/2, 0.2% NH3(aq.) to 95/5, 0.5% NH3(aq.))
  7. customto give
  8. additiona mixture of diastereoisomers 1 and 2 of C24 (231 mg, 52% yield, mixture of diasteroisomers)

Sources & evidence

ORD record
ord-170c2435062f4b65a2c5fa2a8d499746
Source dataset
uspto-grants-2013_06
Patent number
US08455646B2

Reaction notes

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