Hydrochloric Acid → Z-Leu-phe-OH

HRID 467303Notes

Reaction equation

HRID 467303 reaction equation
C[O:2][C:3](=[O:31])[C@H:4]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[NH:5][C:6](=[O:23])[C@H:7]([CH2:19][CH:20]([CH3:22])[CH3:21])[NH:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].O1CCOCC1.O.[OH-].[Na+].Cl>C(OCC)(=O)C>[CH2:12]([O:11][C:9]([NH:8][C@H:7]([C:6]([NH:5][C@H:4]([C:3]([OH:31])=[O:2])[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:23])[CH2:19][CH:20]([CH3:21])[CH3:22])=[O:10])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 13968141N-benzyloxycarbonyl-L-leucyl-L-phenylalanine methyl esterHCID 218864351,4-Dioxane--water (1/1)

Product 1

HCID 7408339Z-Leu-phe-OHYield 99.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of N-benzyloxycarbonyl-L-leucine (2.7 g, 10.2 mmol), L-phenylalanine methyl ester hydrochloride (2.2 g, 10.2 mmol), and triethylamine (1.4 mL, 10.2 mmol) in dry THF (150 mL) was added N-ethyl-N'-dimethylaminopropyl-carbodiimide (EDCI) (2.2 g, 11.2 mmol) with stirring at room temperature. After the mixture was stirred overnight at room temperature, it was rotary evaporated. The residue was mixed with ethyl acetate and then washed successively with water, 1N HCl, and brine; the solution was dried (MgSO4) and evaporated to give a white solid residue. Recrystallization (EtOAc-hexane) gave 2.9 g (66%) of N-benzyloxycarbonyl-L-leucyl-L-phenylalanine methyl ester, m.p. 91°-93° C. A mixture of this ester (2.8 g, 6.6 mmol) in 2:1 dioxane-water (150 mL) was treated at 0° C. with 1N NaOH solution (7.3 mmol). After stirring the solution for 2-3 hours at room temperature, it was acidified at 0° C. by the addition of 1N HCl, and then rotary evaporated. The residue was mixed with ethyl acetate and then washed successively with water, 1N HCl, and brine; the solution was dried (MgSO4) and evaporated to give 2.7 g of N-benzyloxycarbonyl-L-leucyl-L-phenylalanine as a white solid, m.p. 120°-122° C.

Workup

  1. washwashed successively with water, 1N HCl, and brine
  2. dry with materialthe solution was dried (MgSO4)
  3. customevaporated

Sources & evidence

ORD record
ord-06cdb19e71804e9cac04bf6646d817fb
Source dataset
uspto-grants-1992_10
Patent number
US05158936

Reaction notes

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