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

HRID 456487Notes

Reaction equation

HRID 456487 reaction equation
[NH2:1][C@H:2]([C:7]([OH:9])=O)[CH2:3][CH2:4][S:5][CH3:6].Cl.CN(C)CCCN=C=NCC.[CH:22]1[CH:23]=[CH:24][C:25]2N(O)N=N[C:26]=2[CH:27]=1.[C:32]([O:36][C:37](=[O:41])[C@H:38]([CH3:40])[NH2:39])([CH3:35])([CH3:34])[CH3:33]>CN(C=O)C.C(N(CC)CC)C>[CH2:32]([O:36][C:37]([NH:1][C@H:2]([C:7]([NH:39][C@H:38]([C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:41])[CH3:40])=[O:9])[CH2:3][CH2:4][S:5][CH3:6])=[O:41])[C:26]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:27]=1

Participants

7

Reactant 4

HCID 6137L-MethionineHCID 757711-HydroxybenzotriazoleHCID 89016L-Alanine 1,1-dimethylethyl esterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Z-Protected L-methionine (10 g) was dissolved in DMF (200 ml) and 1-[3-(dimethylamino)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 18h. 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 18h
  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-586e2c106b1f4728944b865e8626da24
Source dataset
uspto-grants-2007_03
Patent number
US07186717B2

Reaction notes

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