L-Methionine → tert-Butyl N-[(benzyloxy)carbonyl]-L-methionyl-L-alaninate

HRID 1990685Notes

Reaction equation

HRID 1990685 reaction equation
[NH2:1][C@H:2]([C:7]([OH:9])=O)[CH2:3][CH2:4][S:5][CH3:6].[CH:10]1[CH:11]=[CH:12][C:13]2N(O)N=N[C:14]=2[CH:15]=1.C(N(CC)CC)C.[C:27]([O:31][C:32](=[O:36])[C@H:33]([CH3:35])[NH2:34])([CH3:30])([CH3:29])[CH3:28]>CN(C=O)C>[CH2:27]([O:31][C:32]([NH:1][C@H:2]([C:7]([NH:34][C@H:33]([C:32]([O:31][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:36])[CH3:35])=[O:9])[CH2:3][CH2:4][S:5][CH3:6])=[O:36])[C:14]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:15]=1

Participants

6

Reactant 4

HCID 6137L-MethionineHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 89016L-Alanine 1,1-dimethylethyl ester

Product 1

HCID 16124765tert-Butyl N-[(benzyloxy)carbonyl]-L-methionyl-L-alaninateYield 109.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Z-Protected L-methionine (10 g) was dissolved in DMF (200 ml) and 1-[3-(dimethylamino)propyol]-3-ethylcarbodiimide hydrochloride (8.13 g) was added followed by HOBT (5.72 g) and triethylamine (19.7 ml). The mixture was stirred for 1 h then L-alanine tert-butyl ester (7.7 g) was added and stirring continued for 18 h. The mixture was concentrated under reduced pressure and partitioned between diethyl ether and water. The separated organic phase was washed with hydrochloric acid (1M), saturated sodium bicarbonate solution and brine, dried (over magnesium sulphate) and concentrated under reduced pressure to give the title compound (11.9 g) as an orange oil which crystallised on standing.

Workup

  1. stirringstirring
  2. waitcontinued for 18 h
  3. concentrationThe mixture was concentrated under reduced pressure
  4. custompartitioned between diethyl ether and water
  5. washThe separated organic phase was washed with hydrochloric acid (1M), saturated sodium bicarbonate solution and brine
  6. dry with materialdried (over magnesium sulphate)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5193d548512e4a4b923864d7b0df0117
Source dataset
uspto-grants-2010_01
Patent number
US07645338B2

Reaction notes

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