Benzyl Alcohol → HCID 131721200, compound

HRID 1954684Notes

Reaction equation

HRID 1954684 reaction equation
[N:1]1([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:25][CH2:24][CH2:23][CH2:22][C@@H:2]1[C:3]([N:5]([CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[O:4].[Li+].[OH-].C(O)[C:39]1[CH:44]=[CH:43]C=[CH:41][CH:40]=1.CN(C1C=CC=CN=1)C.C1(N=C=NC2CCCCC2)CCCCC1>O1CCOCC1.O.ClCCl>[N:1]1([C:26]([O:28][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:27])[CH2:25][CH2:24][CH2:23][CH2:22][C@@H:2]1[C:3]([N:5]([CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:20][C:21]1[CH:43]=[CH:44][CH:39]=[CH:40][CH:41]=1)=[O:18])[CH2:6][C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])=[O:4]

Participants

9

Reactant 5

HCID 244Benzyl AlcoholHCID 3939Lithium HydroxideHCID 10868DicyclohexylcarbodiimideHCID 218852-DimethylaminopyridineHCID 131721201HCID 131721201, compound

Product 1

HCID 131721200HCID 131721200, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of Cbz-D-hPro-N(CH2CH2CH2COOEt)Gly-O-t-Bu (7.4 g, 15 mmol) in dioxane (200 mL) was added a solution of LiOH (0.8 g, 19 mmol) in H2O (100 mL). The mixture was allowed to stir for 2 hours at room temperature and was then concentrated to a volume of 10 mL. The residue was diluted to 100 mL with H2O and washed with diethyl ether. The aqueous layer was acidified to pH 3 with 5N HCl and then was extracted twice with ethyl acetate (50 mL). The organic layer was dried (MgSO4) and concentrated in vacuo to give a colorless oil. The oil was dissolved in dichloromethane and to this solution was added benzyl alcohol (2.5 mL, 23 mmol), dimethylaminopyridine (1.8 g, 15 mmol) and dicyclohexylcarbodiimide (3.1 g, 15 mmol) . After stirring for 16 hours at room temperature, a white precipitate was removed by filtration and the filtrate was concentrated in vacuo. The residue was chromatographed over silica gel, eluting with a step gradient of hexanes through 50% ethyl acetate/hexanes. Fractions containing product (based on TLC) were combined and concentrated to give 6.1 g (74%) of a colorless oil.

Workup

  1. concentrationwas then concentrated to a volume of 10 mL
  2. additionThe residue was diluted to 100 mL with H2O
  3. washwashed with diethyl ether
  4. extractionwas extracted twice with ethyl acetate (50 mL)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto give a colorless oil
  8. stirringAfter stirring for 16 hours at room temperature
  9. customa white precipitate was removed by filtration
  10. concentrationthe filtrate was concentrated in vacuo
  11. customThe residue was chromatographed over silica gel
  12. washeluting with a step gradient of hexanes through 50% ethyl acetate/hexanes
  13. additionFractions containing product (based on TLC)
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-7da8f381704e4f66bd8ae0e582d4f436
Source dataset
uspto-grants-2000_09
Patent number
US06124277

Reaction notes

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