Hydrochloric Acid → HCID 86748261, compound

HRID 2380114Notes

Reaction equation

HRID 2380114 reaction equation
C(OC([NH:8][C@@H:9]([CH2:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[C@@H:10]([OH:24])[CH2:11][C@@H:12]([C:20]([OH:23])([CH3:22])[CH3:21])[C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:14])=O)(C)(C)C.Cl.[C:33]([O:37][C:38]([NH:40][C@H:41]([C:48](O)=[O:49])[CH2:42][C:43]1[N:44]=[CH:45][S:46][CH:47]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34].P(C#N)(OCC)(OCC)=O>O1CCOCC1.O1CCCC1.C(N(CC)CC)C>[C:33]([O:37][C:38]([NH:40][C@H:41]([C:48]([NH:8][C@@H:9]([CH2:25][CH:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1)[C@@H:10]([OH:24])[CH2:11][C@@H:12]([C:20]([OH:23])([CH3:21])[CH3:22])[C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:14])=[O:49])[CH2:42][C:43]1[N:44]=[CH:45][S:46][CH:47]=1)=[O:39])([CH3:35])([CH3:36])[CH3:34]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 76257Diethyl cyanophosphonateHCID 2734486(S)-2-((tert-Butoxycarbonyl)amino)-3-(thiazol-4-yl)propanoic acidHCID 14989086HCID 14989086, compound

Product 1

HCID 86748261HCID 86748261, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 309 mg (0.698 mmole) of (2S, 4S, 5S)-5-(t-butoxycarbonylamino)-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-butylhexanamide (prepared as described in Preparation 29) in 6 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature for 30 minutes under an atmosphere of nitrogen. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and then benzene was added to the residue. The solvent was removed by distillation under reduced pressure from the resulting solution. The same operation was repeated, in total, three times, and the resulting residue was then dried by evaporation under reduced pressure for 8 hours. At the end of this time, 200.6 mg (0.737 mmole) of N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanine were added to a suspension of the dried material in 15 ml of anhydrous tetrahydrofuran, and then 0.13 ml (0.858 mmole) of 95% diethyl cyanophosphate and 0.3 ml of triethylamine were added to the resulting mixture, whilst ice-cooling and under an atmosphere of nitrogen. The mixture was then stirred for 5 hours, after which the solvent was removed by distillation under reduced pressure and the residue was purified by medium pressure silica gel column chromatography (using a 20:1 by volume mixture of methylene chloride and methanol as eluent), followed by recrystallization from a mixture of methylene chloride and diisopropyl ether, to give 457.8 mg or the title compound as white crystals.

Workup

  1. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  2. additionbenzene was added to the residue
  3. customThe solvent was removed by distillation under reduced pressure from the resulting solution
  4. customthe resulting residue was then dried by evaporation under reduced pressure for 8 hours
  5. temperaturecooling and under an atmosphere of nitrogen
  6. stirringThe mixture was then stirred for 5 hours
  7. customafter which the solvent was removed by distillation under reduced pressure
  8. customthe residue was purified by medium pressure silica gel column chromatography (
  9. additionby volume mixture of methylene chloride and methanol as eluent),
  10. customfollowed by recrystallization from a mixture of methylene chloride and diisopropyl ether
  11. customto give 457.8 mg

Sources & evidence

ORD record
ord-d83d49b45a96400492570c173f71b5c4
Source dataset
uspto-grants-1994_11
Patent number
US05364844

Reaction notes

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