N-[(1,1-Dimethylethoxy)carbonyl]-L-alanyl-L-proline phenylmethyl ester → Boc-ala-pro-OH

HRID 2107783Notes

Reaction equation

HRID 2107783 reaction equation
[NH:1]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:2]([C:4]([N:6]1[CH2:20][CH2:19][CH2:18][C@H:7]1[C:8]([O:10]CC1C=CC=CC=1)=[O:9])=[O:5])[CH3:3]>CO.[Pd]>[NH:1]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[C@H:2]([C:4]([N:6]1[CH2:20][CH2:19][CH2:18][C@H:7]1[C:8]([OH:10])=[O:9])=[O:5])[CH3:3]

Participants

4

Reactant 1

HCID 13068139N-[(1,1-Dimethylethoxy)carbonyl]-L-alanyl-L-proline phenylmethyl ester

Product 1

HCID 11902919Boc-ala-pro-OHYield 60.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Boc-Ala-Pro-boroPro-pinacol was prepared by coupling Boc-Ala-Pro-OH to H-boroPro-pinacol. First, the dipeptide, Boc-Ala-Pro-OBzl, was prepared by the mixed anhydride procedure. Boc-Ala-OH (10 g, 52.8 mmoles) was reacted with N-methylmorpholine (5.8 ml, 52.8 mmoles) and isobutyl chloroformate (6.8 ml, 52.8 mmole) for 5 minutes in 50 ml of THF at -20°. The reaction mixture and additional N-methylmorpholine (5.8 ml) were added to H-Pro-OBzl.HCL (12.8 g, 52.8 mmoles) dissolved in 50 ml of cold chloroform. After the mixture was stirred for 1 hour at -20° C. and 2 hours at room temperature, it was filtered and the filtrate evaporated. The residue was dissolved in ethyl acetate and washed sequentially with 0.2N hydrochloric acid, 5% aqueous NaCO3, and saturated aqueous NaCl. The organic phase was dried over anhydrous Na2SO4, filtered, and evaporated to yield Boc-Ala-Pro-OBzl as an oil (14.1 g). The benzyl ester protecting group was removed by dissolving Boc-Ala-Pro-OBzl (35 g, 92.8 mmoles) in 200 ml of methanol and hydrogenating for 1 hour in the presence of 0.5 g of 10% Pd/C. The catalyst was removed by filtration and the solvent evaporated. The residue was crystallized from ethyl acetate to yield 16.1 g of Boc-Ala-Pro-OH (mp 153.5°-154.5° C.).

Workup

  1. customThe benzyl ester protecting group was removed
  2. customThe catalyst was removed by filtration
  3. customthe solvent evaporated
  4. customThe residue was crystallized from ethyl acetate

Sources & evidence

ORD record
ord-0cd166bff29c4cbca346739a3f0a6f56
Source dataset
uspto-grants-1990_06
Patent number
US04935493

Reaction notes

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