Ethyl 3-(6-aminopyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)propionate → (R)-3-(6-Amino-pyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)-propionic acid ethyl ester

HRID 512742Notes

Reaction equation

HRID 512742 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH:5]([C:14]1[N:15]=[CH:16][N:17]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:18]=1)[CH2:6][C:7]1[CH:8]=[N:9][C:10]([NH2:13])=[CH:11][CH:12]=1)[CH3:2].C(OC(=O)[C@H](C1N=CN(C2CCCCC2)C=1)CC1C=NC(N)=CC=1)C>C(O)C>[CH2:1]([O:3][C:4](=[O:25])[C@@H:5]([C:14]1[N:15]=[CH:16][N:17]([CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]2)[CH:18]=1)[CH2:6][C:7]1[CH:8]=[N:9][C:10]([NH2:13])=[CH:11][CH:12]=1)[CH3:2]

Participants

4

Reactant 2

HCID 11544682Ethyl 3-(6-aminopyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)propionateHCID 89587960(S)-3-(6-Amino-pyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)-propionic acid ethyl ester

Product 1

HCID 71565468(R)-3-(6-Amino-pyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Batches containing 540 g of 3-(6-Amino-pyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)-propionic acid ethyl ester were filled into a column containing 20 kg of Chiralpack AD 20 μm (Ciral Technologies Europe, France) as a chiral stationary phase. Ethanol was pumped through the column until no more (S)-3-(6-Amino-pyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)-propionic acid ethyl ester was eluted. Then a mixture containing ethanol with 0.4% of trifluoroacetic acid were pumped through the column and fractions containing (R)-3-(6-Amino-pyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)-propionic acid ethyl ester were collected. The received title compound showed a purity of 91.7% and an ee of 99.2%. The purity was determined by the chromatography described in Example 8.

Workup

  1. additionwere filled into a column
  2. additioncontaining 20 kg of Chiralpack AD 20 μm (Ciral Technologies Europe, France) as a chiral stationary phase
  3. washwas eluted
  4. additionThen a mixture containing ethanol with 0.4% of trifluoroacetic acid
  5. additioncontaining (R)-3-(6-Amino-pyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)-propionic acid ethyl ester
  6. customwere collected

Sources & evidence

ORD record
ord-8ea77a01e91f43c3bd779b664baa048f
Source dataset
uspto-grants-2015_08
Patent number
US09102657B2

Reaction notes

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