Hydrochloric Acid → (2S)-N-((1S,2S)-3-{(2S,3R)-2-[N-(tert-butyl)carbamoyl]-3-hydroxypyrrolidinyl}-2-hydroxy-3-oxo-1-benzylpropyl)-3-carbamoyl-2-[(phenylmethoxy)carbonylamino]propanamide

HRID 1780240Notes

Reaction equation

HRID 1780240 reaction equation
Cl.C(O[C:7]([N:9]1[CH2:20][CH2:19][C@@H:18]([O:21][Si](C(C)(C)C)(C)C)[C@H:10]1[C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:8])(C)(C)C.[CH2:29]([O:36][C:37]([NH:39][C@H:40]([C:45]([NH:47][C@@H:48]([CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[C@H:49]([OH:53])C(O)=O)=[O:46])[CH2:41][C:42](=[O:44])[NH2:43])=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O1CCOCC1.CO>[CH2:29]([O:36][C:37]([NH:39][C@H:40]([C:45]([NH:47][C@@H:48]([CH2:54][C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)[C@H:49]([OH:53])[C:7]([N:9]1[CH2:20][CH2:19][C@@H:18]([OH:21])[C@H:10]1[C:11]([NH:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])=[O:8])=[O:46])[CH2:41][C:42](=[O:44])[NH2:43])=[O:38])[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 22872710(3R)-1-t-butoxycarbonyl-N-t-butyl-3-t-butyldimethylsilyloxy-L-prolinamideHCID 57125825(2S,3S)-3-(N2-benzyloxycarbonyl-L-asparaginyl)amino-2-hydroxy-4-phenylbutyric acid

Product 1

HCID 473132(2S)-N-((1S,2S)-3-{(2S,3R)-2-[N-(tert-butyl)carbamoyl]-3-hydroxypyrrolidinyl}-2-hydroxy-3-oxo-1-benzylpropyl)-3-carbamoyl-2-[(phenylmethoxy)carbonylamino]propanamideYield 41.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

1.5 ml of a 4N solution of hydrogen chloride in dioxane were added to a solution of 50 mg (0.13 mmol) of (3R)-1-t-butoxycarbonyl-N-t-butyl-3-t-butyldimethylsilyloxy-L-prolinamide (prepared as described in Preparation 12) in 0.5 ml of methanol, and the mixture was stirred at room temperature for 1 hour. The solvent was removed by distillation under reduced pressure, and the resulting residue was mixed with benzene. The excess hydrogen chloride was then removed by distillation as an azeotrope with the benzene. The resulting residue was dried in vacuo for 2 hours and the whole of the resulting (3E)-N-t-butyl-3-t-butyldimethylsilyloxy-L-prolinamide hydrochloride was reacted with 55 mg (0.13 mmol) of (2S,3S)-3-(N2 -benzyloxycarbonyl-L-asparaginyl)amino-2-hydroxy-4-phenylbutyric acid (prepared as described in Preparation 1) following a procedure similar to that described in Example 1, to obtain 33 mg of the title compound as a white powder, melting at 109°-112° C.

Workup

  1. customThe solvent was removed by distillation under reduced pressure
  2. additionthe resulting residue was mixed with benzene
  3. customThe excess hydrogen chloride was then removed by distillation as an azeotrope with the benzene
  4. customThe resulting residue was dried in vacuo for 2 hours

Sources & evidence

ORD record
ord-4974866c2f4c442fb06f2d9814afd204
Source dataset
uspto-grants-1997_05
Patent number
US05629406

Reaction notes

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