Hydrochloric Acid → HCID 86748258, compound

HRID 2380098Notes

Reaction equation

HRID 2380098 reaction equation
C(O[C:6]([NH:8][C@H:9]([C@H:14]1[O:18][C:17](=[O:19])[C@H:16]([C:20]([OH:23])([CH3:22])[CH3:21])[CH2:15]1)[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])(C)(C)C.Cl.[C:25]([O:29][C:30]([NH:32][C@H:33](C(O)=O)[CH2:34][C:35]1[N:36]=[CH:37][S:38][CH:39]=1)=[O:31])([CH3:28])([CH3:27])[CH3:26].P([C:51]#[N:52])(OCC)(OCC)=O.C(N([CH2:58][CH3:59])CC)C.O1CCO[CH2:62][CH2:61]1>>[C:25]([O:29][C:30]([NH:32][C@H:33]([C:6]([NH:8][C@@H:9]([CH2:10][CH:11]([CH3:12])[CH3:13])[C@@H:14]([OH:18])[CH2:15][C@@H:16]([C:20]([OH:23])([CH3:21])[CH3:22])[C:17]([NH:52][CH2:51][CH:58]([CH3:59])[CH2:61][CH3:62])=[O:19])=[O:7])[CH2:34][C:35]1[N:36]=[CH:37][S:38][CH:39]=1)=[O:31])([CH3:26])([CH3:27])[CH3:28]

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 76257Diethyl cyanophosphonateHCID 2734486(S)-2-((tert-Butoxycarbonyl)amino)-3-(thiazol-4-yl)propanoic acidHCID 14483174HCID 14483174, compound

Product 1

HCID 86748258HCID 86748258, compoundYield 85%

Procedure

Following a procedure similar to that described in Example 1, a mixture of 260 mg (0.62 mmoles) of (3S, 5S)-5-[(1S)-1-(N-t-butoxycarbonylamino)-3-methylbutyl]-3-(1-hydroxy-1-methylethyl)dihydrofuran-2(3H)-one (prepared as described in Preparation 9) in 5 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature for 30 minutes. At the end of this time, the solvent was removed by distillation under reduced pressure, and diethyl ether was added to the residue. The solvent was then again removed by distillation under reduced pressure. This operation was repeated in total three times, after which the residue was dried under vacuum for 8 hours. At the end of this time, the dried material was suspended in 5 ml of anhydrous tetrahydrofuran, and 187 mg (0.69 mmoles) of N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanine were added to the resulting suspension, followed by 0.11 ml (0.73 mmoles) of 95% diethyl cyanophosphate and 0.19 ml (1.36 mmoles) of triethylamine, all whilst ice-cooling and under an atmosphere of nitrogen. The mixture was then stirred for 6 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), to give 303 mg (yield 85%) of the title compound as an amorphous substance.

Workup

  1. customAt the end of this time, the solvent was removed by distillation under reduced pressure, and diethyl ether
  2. additionwas added to the residue
  3. customThe solvent was then again removed by distillation under reduced pressure
  4. customafter which the residue was dried under vacuum for 8 hours
  5. temperatureall whilst ice-cooling and under an atmosphere of nitrogen
  6. stirringThe mixture was then stirred for 6 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),

Sources & evidence

ORD record
ord-02fd7291ff9d4875ba6e88233c1eb96d
Source dataset
uspto-grants-1994_11
Patent number
US05364844

Reaction notes

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