Trifluoroacetic acid → HCID 86743724, compound

HRID 330625Notes

Reaction equation

HRID 330625 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18][CH2:19][CH2:20][C:21](=O)[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28]([O:35][C:36](=[O:61])[C@@H:37]1[CH2:41][CH2:40][CH2:39][N:38]1[C:42](=[O:60])[C@H:43]([CH2:45][CH2:46][CH2:47][CH2:48][NH:49][C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51])[NH2:44])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.FC(F)(F)C(O)=O.C([BH3-])#N.[Na+]>C(O)C.C(N(CC)CC)C>[CH2:28]([O:35][C:36](=[O:61])[C@@H:37]1[CH2:41][CH2:40][CH2:39][N:38]1[C:42](=[O:60])[C@H:43]([CH2:45][CH2:46][CH2:47][CH2:48][NH:49][C:50]([O:52][CH2:53][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)=[O:51])[NH:44][C@@H:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:20][CH2:19][CH2:18][CH2:17][CH:14]1[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12][CH2:13]1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydrideHCID 13817563Ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-oxohexanoateHCID 70070228HCID 70070228, compound

Product 1

HCID 86743724HCID 86743724, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8471TriethylamineSolvent

Procedure

A solution of ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-oxohexanoate [prepared according to Chem. Pharm. Bull, 34, 3747 (1986)] (7.4 g) and Nε -benzyloxycarbonyl-L-lysyl-L-proline benzylester.trifluoroacetic acid salt (4.6 g) in ethanol (40 ml) is adjusted to pH 5 with triethylamine. To this solution is added 2 g of molecular sieves, and the reaction mixture is stirred for 30 minutes. A solution of sodiumcyanoborohydride (1.4 g) in ethanol (40 ml) is dropped therein under stirring for 5 hours, and is kept stirring for further one night. The ethanol is distilled under reduced pressure, thereafter the residue is transferred to ethyl acetate. The ethyl acetate layer is washed with water, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. To the residue ether is added. The ether layer is washed with water and then ether is distilled under reduced pressure. The residue is applied to silica gel chromatography (ethyl acetate:hexane=2:1) to obtain, from the first effluence, 1.34 g of Nα -[1(R)-ethoxycarbonyl- 5-(1-benzyloxycarbonyl-4-piperidyl)pentyl]-Nε -benzyloxycarbonyl-L-lysyl-L-proline benzylester (Rf=0.62, expansive solvent, F), and from the following effluence, 1.15 g of Nα -[1(S)ethoxycarbonyl-5-(1-benzyloxycarbonyl-4-piperidyl)pentyl]-Nε -benzyloxycarbonyl-L-proline benzylester (Rf=0.52, expansive solvent, F).

Workup

  1. additionTo this solution is added 2 g of molecular sieves
  2. stirringunder stirring for 5 hours
  3. stirringis kept stirring for further one night
  4. distillationThe ethanol is distilled under reduced pressure
  5. washThe ethyl acetate layer is washed with water
  6. dry with materialdried with anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. additionTo the residue ether is added
  9. washThe ether layer is washed with water
  10. distillationether is distilled under reduced pressure

Sources & evidence

ORD record
ord-a05a83f1b3c542dd92d282d969af1b5f
Source dataset
uspto-grants-1990_01
Patent number
US04897483

Reaction notes

Loading…