Triethylamine → HCID 10372347, compound

HRID 1194981Notes

Reaction equation

HRID 1194981 reaction equation
Cl.[C@H:2]12[CH2:9][CH2:8][CH2:7][C@H:6]1[CH2:5][C@@H:4]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[NH:3]2.Cl.[CH2:21]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([CH2:37][CH2:38][CH2:39][CH2:40][C@H:41]([NH:47][C@H:48]([C:50](O)=[O:51])[CH3:49])[C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:33][CH2:32]1)=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(CC)CC)C.P(C#N)(=O)(OCC)OCC>CN(C)C=O.O>[CH2:21]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([CH2:37][CH2:38][CH2:39][CH2:40][C@H:41]([NH:47][C@H:48]([C:50]([N:3]2[C@H:4]([C:10]([O:12][CH2:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[O:11])[CH2:5][C@H:6]3[C@@H:2]2[CH2:9][CH2:8][CH2:7]3)=[O:51])[CH3:49])[C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:33][CH2:32]1)=[O:30])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 76257Diethyl cyanophosphonateHCID 13216857Benzyl octahydrocyclopenta[b]pyrrole-2-carboxylate--hydrogen chloride (1/1)HCID 18631457HCID 18631457, compound

Product 1

HCID 10372347HCID 10372347, compoundYield 37.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In 10 ml of N,N-dimethylformamide are dissolved 0.56 g of benzyl (S,S,S)-2-azabicyclo[3,3,0]octane-3-carboxylate. hydrochloride and 0.5 g of N-[(S)-5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]-L-alanine.hydrochloride, and 0.3 g of triethylamine is added to the solution under ice-cooling with stirring, followed by addition of 0.5 ml of diethyl phosphorocyanidate. After stirring for 30 minutes, there is added to the mixture 0.1 g of triethylamine, followed by stirring for 30 minutes and at room temperature for 1 hour. The reaction mixture is diluted with 100 ml of water and extracted with 100 ml of ethyl acetate. The extract is washed with 5% aqueous phosphoric acid and water, successively, and dried over anhydrous magnesium sulfate. The solvent is distilled off under reduced pressure, and the residue is purified by silica gel column chromatography (hexane:acetone=3:1) to give 0.26 g of benzyl (S,S,S)-2-[N-[(S)-5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]-L-alanyl]-2-azabicyclo[3,3,0]octane-3-carboxylate as a colorless oil.

Workup

  1. additionis added to the solution under ice-
  2. temperaturecooling
  3. stirringAfter stirring for 30 minutes
  4. stirringby stirring for 30 minutes and at room temperature for 1 hour
  5. extractionextracted with 100 ml of ethyl acetate
  6. washThe extract is washed with 5% aqueous phosphoric acid and water
  7. dry with materialsuccessively, and dried over anhydrous magnesium sulfate
  8. distillationThe solvent is distilled off under reduced pressure
  9. customthe residue is purified by silica gel column chromatography (hexane:acetone=3:1)

Sources & evidence

ORD record
ord-2af59b5836ff4b34b6be56e12efd4ed6
Source dataset
uspto-grants-1989_03
Patent number
US04816466

Reaction notes

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