Dichloromethane → N-[N-[(3S)-3-Amino-2-hydroxybutyl]-L-phenylalanvl]-L-leucine, dihydrochloride

HRID 1583677Notes

Reaction equation

HRID 1583677 reaction equation
C(OC([NH:8][C@@H:9]([CH3:37])[CH:10]([OH:36])[CH2:11][NH:12][C@H:13]([C:21]([NH:23][C@H:24]([C:29]([O:31]C(C)(C)C)=[O:30])[CH2:25][CH:26]([CH3:28])[CH3:27])=[O:22])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=O)(C)(C)C.FC(F)(F)C(O)=O.[Cl:45]CCl>>[ClH:45].[ClH:45].[NH2:8][C@@H:9]([CH3:37])[CH:10]([OH:36])[CH2:11][NH:12][C@H:13]([C:21]([NH:23][C@H:24]([C:29]([OH:31])=[O:30])[CH2:25][CH:26]([CH3:28])[CH3:27])=[O:22])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 13933328N-[(3S)-3-[[(t-Butyloxy)carbonyl]amino]-2-hydroxybutyl]-L-phenylalanyl-L-leucine, t-butyl ester

Product 1

HCID 131714412N-[N-[(3S)-3-Amino-2-hydroxybutyl]-L-phenylalanvl]-L-leucine, dihydrochloride

Procedure

To a solution of N-[N-[(3S)-3-[[(t-butyloxy)carbonyl]amino]-2-hydroxybutyl]-L-phenylalanyl-L-leucine, t-butyl ester (faster isomer) (0.33 g, 0.64 mmol) in 3.5 ml of dichloromethane was added trifluoroacetic acid (2 ml). The resulting solution was stoppered and allowed to stand for 1 hour at room temperature, and the solvent was then evaporated. Analysis of the residue by 13C-NMR showed a considerable amount of unreacted t-butyl ester. The recovered material was treated with 10 ml of ~1.5N hydrogen chloride in acetic acid for 1.5 hours at room temperature. The solvent was evaporated (<25° C., vacuum pump) and the residue was triturated with ether yielding a white solid. Analysis by 13C-NMR again revealed t-butyl resonances, although diminished in intensity. The aforementioned hydrogen chloride/acetic acid treatment was repeated three more times, finally yielding 200 mg of the title compound as a white solid, melting point 174°-177° C. (changes form 127°-131° C.).

Workup

  1. customthe solvent was then evaporated
  2. additionThe recovered material was treated with 10 ml of ~1.5N hydrogen chloride in acetic acid for 1.5 hours at room temperature
  3. customThe solvent was evaporated (<25° C., vacuum pump)
  4. customthe residue was triturated with ether yielding a white solid
  5. customfinally yielding

Sources & evidence

ORD record
ord-b9e36a6d7b314b888cdd14d31481f448
Source dataset
uspto-grants-1985_11
Patent number
US04552866

Reaction notes

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