Hydrochloric Acid → N-[(R)-1-ethoxycarbonyl-2-heptylthioethyl]-alanyl-(S)-prolyl-(S)-proline t-butyl ester

HRID 476984Notes

Reaction equation

HRID 476984 reaction equation
[C:1]([O:5][C:6](=[O:19])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:18])[C@@H:13]1[CH2:17][CH2:16][CH2:15][NH:14]1)([CH3:4])([CH3:3])[CH3:2].Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[CH2:38]([O:40][C:41]([C@@H:43]([NH:53][C@H:54]([C:56](O)=[O:57])[CH3:55])[CH2:44][S:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])=[O:42])[CH3:39]>CN(C=O)C>[C:1]([O:5][C:6](=[O:19])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:18])[C@@H:13]1[CH2:17][CH2:16][CH2:15][N:14]1[C:56](=[O:57])[C@H:54]([CH3:55])[NH:53][C@H:43]([C:41]([O:40][CH2:38][CH3:39])=[O:42])[CH2:44][S:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 13647905N-[(R)-1-ethoxycarbonyl-2-heptylthioethyl]-alanineHCID 15598548HCID 15598548, compound

Product 1

HCID 70385928N-[(R)-1-ethoxycarbonyl-2-heptylthioethyl]-alanyl-(S)-prolyl-(S)-proline t-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In 25 ml of DMF were dissolved 2.6 g of the β-isomer of N-[(R)-1-ethoxycarbonyl-2-heptylthioethyl]-alanine prepared in Reference Example 29, 2.5 g of (S)-prolyl-(S)-proline t-butyl ester prepared in Reference Example 28, 1.7 g of WSCD.HCl and 1.1 g of HOBt. To the solution was added 3.6 ml of triethylamine while being stirred with ice cooling. The solution was stirred overnight. The reaction mixture was poured into ice water, followed by extraction with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and then with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (a 30:1 mixture of chloroform and methanol as an eluent), giving the title compound as a colorless oil. Yield 3.5 g.

Workup

  1. customprepared in Reference Example 28, 1.7 g of WSCD
  2. stirringThe solution was stirred overnight
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe extract was washed with a saturated aqueous solution of sodium hydrogencarbonate
  5. dry with materialwith a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (
  8. additiona 30:1 mixture of chloroform and methanol as an eluent),

Sources & evidence

ORD record
ord-c9a580839c3548e19f3d63158c4f3bd2
Source dataset
uspto-grants-1989_12
Patent number
US04886813

Reaction notes

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