Hydrochloric Acid → 1,3-Thiazol-5-ylmethyl N-((1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentyl)carbamate

HRID 1489987Notes

Reaction equation

HRID 1489987 reaction equation
C(OC([NH:8][C@@H:9]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:10][C@H:11]([OH:30])[C@@H:12]([NH:20][C:21]([O:23][CH2:24][C:25]1[S:29][CH:28]=[N:27][CH:26]=1)=[O:22])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=O)(C)(C)C.Cl>O1CCOCC1>[NH2:8][C@@H:9]([CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[CH2:10][C@H:11]([OH:30])[C@@H:12]([NH:20][C:21]([O:23][CH2:24][C:25]1[S:29][CH:28]=[N:27][CH:26]=1)=[O:22])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 22858342Thiazol-5-ylmethyl ((1S,2S,4S)-1-benzyl-4-(((1,1-dimethylethoxy)carbonyl)amino)-2-hydroxy-5-phenylpentyl)carbamate

Product 1

HCID 111019781,3-Thiazol-5-ylmethyl N-((1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentyl)carbamateYield 99.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent3×

Procedure

The product of Example 69A (6.43 g, 12.23 mmoles) was dissolved in 25 mL dioxane at room temperature under nitrogen atmosphere. To this stirred solution was added 20.25 mL of 4N HCl in dioxane, and after approximately 10 min thick precipitate formed. An additional 10 mL of dioxane was added to loosen up the slurry. This mixture was stirred for 1 h and then filtered. The filter cake of the product bis-HCl salt was washed with 20 mL dioxane, air dried, and then dissolved in 175 mL water. To this solution was added 175 mL ethyl acetate and the two phase mixture rapidly stirred. The pH of this mixture was adjusted to pH=10 by the dropwise addition of 3N NaOH to the rapidly stirred mixture. The organic layer was isolated, washed with brine (150 mL), and dried over Na2SO4. The solvent was removed to afford 5.18 g (99%) of the desired product as a clear oil. H1NMR (CDCl3) δ 8.81 (s, 1H), 7.87 (s, 1H), 7.35-7.05 (m, 10H), 5.33 (d, 1H, J=9.3 Hz), 5.28 (m,2H), 3.81 (m, 1H), 3.72 (m, 1H), 3.01 (m, 1H), 2.88 (m, 2.78 (dd, 1H, J=13.5, 5.1 Hz), 2.39 (dd, 1H, J=9.0, 4.5 Hz), 1.57-1.30 (m, 2H) 2H). ClMS m/z 426 (M+H)+.

Workup

  1. customafter approximately 10 min thick precipitate formed
  2. filtrationfiltered
  3. washThe filter cake of the product bis-HCl salt was washed with 20 mL dioxane, air
  4. customdried
  5. dissolutiondissolved in 175 mL water
  6. additionTo this solution was added 175 mL ethyl acetate
  7. stirringthe two phase mixture rapidly stirred
  8. additionThe pH of this mixture was adjusted to pH=10 by the dropwise addition of 3N NaOH to the rapidly stirred mixture
  9. customThe organic layer was isolated
  10. washwashed with brine (150 mL)
  11. dry with materialdried over Na2SO4
  12. customThe solvent was removed

Sources & evidence

ORD record
ord-f9514de3a55d4c63bceb448bb0c10991
Source dataset
uspto-grants-1997_10
Patent number
US05679797

Reaction notes

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