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

HRID 349509Notes

Reaction equation

HRID 349509 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 69359995tert-Butyl N-[(benzyloxy)carbonyl]-L-methionyl-D-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-(diemthylamino)propyl]-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 evaporated 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. customThe mixture was evaporated 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-42ddb423040e48ee8ffb86318966643e
Source dataset
uspto-grants-2007_02
Patent number
US07179835B2

Reaction notes

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