2,4,5-Trichlorophenol → Cbz-D-hPro-Pro-OH

HRID 725795

Reaction equation

HRID 725795 reaction equation
[N:1]1([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:9][CH2:8][CH2:7][CH2:6][C@@H:2]1[C:3]([OH:5])=O.ClC1C=C(Cl)C(Cl)=CC=1O.C1(N=C=NC2CCCCC2)CCCCC1.[NH:45]1[CH2:52][CH2:51][CH2:50][C@H:46]1[C:47]([OH:49])=[O:48].C(N(CC)CC)C>C(OCC)(=O)C>[N:1]1([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:9][CH2:8][CH2:7][CH2:6][C@@H:2]1[C:3]([N:45]1[CH2:52][CH2:51][CH2:50][C@H:46]1[C:47]([OH:49])=[O:48])=[O:5]

Participants

7

Reactant 5

HCID 72712,4,5-TrichlorophenolHCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 145742L-ProlineHCID 688346(2R)-1-((Benzyloxy)carbonyl)piperidine-2-carboxylic acid

Product 1

HCID 22854903Cbz-D-hPro-Pro-OH

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Cbz-D-hPro-OH (9.5 g, 36 mmol) was dissolved in ethyl acetate (100 mL) and the solution cooled to 0° C. Added to the solution was 2,4,5-trichlorophenol (7.1 g, 36 mmol) and 1,3-dicyclohexylcarbodiimide (7.4 g, 36 mmol). The reaction was stirred for 1 hour at 0° C. and 1 hour at room temperature. The precipitate was filtered and the filtrate concentrated in vacuo to an oil. The oil was dissolved in pyridine (100 mL), Pro-OH (4.2 g, 36 mmol), and triethylamine (5.0 mL, 36 mmol) were added. The reaction was stirred at room temperature (24 hours). The reaction solvent was removed in vacuo to an oil. The residue was dissolved in water (100 mL), diethyl ether (50 mL) was added and the pH adjusted to 9.5 with 2N sodium hydroxide. The aqueous layer extracted twice with diethyl ether. The aqueous layer separated, the pH adjusted to 2.8 with 3N hydrochloric acid and ethyl acetate (150 mL) was added. The organic layer was separated, dried (MgSO4), and the filtrate evaporated in vacuo to an amorphous solid (11.4 g, 88%).

Workup

  1. additionAdded to the solution
  2. filtrationThe precipitate was filtered
  3. concentrationthe filtrate concentrated in vacuo to an oil
  4. dissolutionThe oil was dissolved in pyridine (100 mL)
  5. stirringThe reaction was stirred at room temperature (24 hours)
  6. customThe reaction solvent was removed in vacuo to an oil
  7. dissolutionThe residue was dissolved in water (100 mL)
  8. additiondiethyl ether (50 mL) was added
  9. extractionThe aqueous layer extracted twice with diethyl ether
  10. customThe aqueous layer separated
  11. additionwas added
  12. customThe organic layer was separated
  13. dry with materialdried (MgSO4)
  14. customthe filtrate evaporated in vacuo to an amorphous solid (11.4 g, 88%)

Sources & evidence

ORD record
ord-f4feab77d2ab456da0547271c4cbf24f
Source dataset
uspto-grants-1998_01
Patent number
US05707966

Linked notes

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