1-Hydroxybenzotriazole → Dicyclohexylcarbodiimide

HRID 2112281Notes

Reaction equation

HRID 2112281 reaction equation
C([C@@H](N[C@H](C(O)=O)C)CCC)(OCC)=O.CCC[C@H](N[C@H](C([N:30]1[C@H:38](C(O)=O)C[C@H:36]2[C@@H:31]1[CH2:32][CH2:33][CH2:34][CH2:35]2)=O)C)C(OCC)=O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([C@@H]1C[C@H:63]2[C@H:58]([CH2:59][CH2:60][CH2:61][CH2:62]2)[NH:57]1)(O)=O.ON1C2C=CC=CC=2N=N1>C(N(CC)CC)C>[CH:58]1([N:57]=[C:38]=[N:30][CH:31]2[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]2)[CH2:63][CH2:62][CH2:61][CH2:60][CH2:59]1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 107807PerindoprilHCID 10015159(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoic acid2×HCID 131727202(2S,3aS,7aS)-2-carboxyperhydroindole, p-toluenesulfonate salt

Product 1

HCID 10868Dicyclohexylcarbodiimide

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Langlois et. al. in published PCT Appln. No. WO 01/58868 disclose a further method for preparation of the (S,S) diastereoisomer of N-[(S)-1-carbethoxybutyl]-(S)-alanine, a key intermediate for perindopril comprising reacting benzyl ester of (2S, 3aS,7aS)-2-carboxyperhydroindole, p-toluenesulfonate salt with (S,S) diastereoisomer of N-[(S)-1-carbethoxybutyl]-(S)-alanine in the presence of 0.4 to 0.6 moles of 1-hydroxybenzotriazole; 1 to 1.2 moles of dicyclohexylcarbodiimide and I mole of triethylamine at 77° C. to give the dipeptide compound, which on debenzylation gives perindopril.

Sources & evidence

ORD record
ord-8e71a438f5384b94a9c5e9bb704a4294
Source dataset
uspto-grants-2009_04
Patent number
US07521566B2

Reaction notes

Loading…