Triethylamine → HCID 70486353, compound

HRID 484749Notes

Reaction equation

HRID 484749 reaction equation
C(N(CC)CC)C.FC(F)(F)C(O)=O.[CH2:15]([S:17]([NH2:20])(=[O:19])=[O:18])[CH3:16].[NH2:21][C@H:22]([C:24]([N:26]1[CH2:33][CH2:32][CH2:31][C@H:27]1[C:28]([OH:30])=[O:29])=[O:25])[CH3:23].O=[C:35]([CH2:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:36]([O:38][CH2:39][CH3:40])=[O:37].C([BH3-])#N.[Na+]>C(O)C>[CH2:15]([S:17]([NH2:20])(=[O:19])=[O:18])[CH3:16].[CH2:39]([O:38][C:36]([CH:35]([NH:21][C@H:22]([C:24]([N:26]1[CH2:33][CH2:32][CH2:31][C@H:27]1[C:28]([OH:30])=[O:29])=[O:25])[CH3:23])[CH2:41][CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)=[O:37])[CH3:40]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 562087Ethyl alpha-oxobenzenebutanoateHCID 5003444Sodium cyanoborohydrideHCID 70486117HCID 70486117, compound

Product 1

HCID 70486353HCID 70486353, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Powdered activated 4 Å molecular sieve (13.5 g.) followed by triethylamine (11.13 ml.) were added to a stirred solution of L-alanyl-L-proline ethanesulphonamide trifluoroacetate (31.1 g.) in ethanol (450 ml.). Ethyl 2-oxo-4-phenylbutyrate (41.0 g.) was then added and the mixture was stirred at laboratory temperature for 30 minutes. A solution of sodium cyanoborohydride (7.7 g.) in ethanol (225 ml.) was then added during 15 hours and the mixture was stirred for a further 10 hours, filtered through a filter-aid and the filtrate was evaporated to dryness under reduced pressure. The residue was partitioned between saturated aqueous sodium carbonate solution (1000 ml.) and diethyl ether (1000 ml.) and the aqueous layer was separated, acidified to pH 3 with concentrated aqueous hydrochloric acid and extracted with methylene chloride. The extract was dried and evaporated to dryness under reduced pressure and the residue was purified by chromatography on a silica gel column using a 9:1 v/v mixture of methylene chloride and methanol as eluant. There were thus obtained the mixed isomers of N-(1-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline ethanesulphonamide in a ratio (as shown by high pressure liquid chromatography) of approximately 11:9 by weight. The isomers were separated by chromatography on a silica gel column using a 99:1 v/v mixture of ethyl acetate and acetic acid as eluant, and there were thus separately obtained N-[(1R)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline ethanesulphonamide, and N-[(1S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline ethane-sulphonamide, both of which were oils, the structures of which were confirmed by proton magnetic resonance and mass spectroscopy. The isomer initially present as 45% by weight of the mixture was considerably more active as an inhibitor of ACE than the other isomer.

Workup

  1. stirringthe mixture was stirred for a further 10 hours
  2. filtrationfiltered through
  3. filtrationa filter-aid
  4. customthe filtrate was evaporated to dryness under reduced pressure
  5. customThe residue was partitioned between saturated aqueous sodium carbonate solution (1000 ml.) and diethyl ether (1000 ml.)
  6. customthe aqueous layer was separated
  7. extractionextracted with methylene chloride
  8. customThe extract was dried
  9. customevaporated to dryness under reduced pressure
  10. customthe residue was purified by chromatography on a silica gel column
  11. additiona 9:1 v/v mixture of methylene chloride and methanol as eluant

Sources & evidence

ORD record
ord-f9346d2815a94029adfa2c056746c150
Source dataset
uspto-grants-1985_08
Patent number
US04533656

Reaction notes

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