4-Methylmorpholine → Boc-(D)-Met-(L)-Ala-OMe

HRID 276755Notes

Reaction equation

HRID 276755 reaction equation
CN1CCOCC1.Cl.[CH3:9][O:10][C:11](=[O:15])[C@H:12]([CH3:14])[NH2:13].C1C=CC2N(O)N=NC=2C=1.CN(C)CCCN=C=NCC.[C:37]([NH:44][C@@H:45]([C:50](O)=[O:51])[CH2:46][CH2:47][S:48][CH3:49])([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38]>CN(C=O)C>[NH:44]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C@@H:45]([C:50]([NH:13][C@H:12]([C:11]([O:10][CH3:9])=[O:15])[CH3:14])=[O:51])[CH2:46][CH2:47][S:48][CH3:49]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 111051N-(tert-Butyloxycarbonyl)-D-methionineHCID 2733257Alanine methyl ester hydrochloride

Product 1

HCID 11024115Boc-(D)-Met-(L)-Ala-OMeYield 77.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-methylmorpholine (5.6 g), L-alanine methyl ester hydrochloride (3.9 g), HOBT (4.6 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (5.3 g) was added to a solution of Boc-(D)-Methionine (7 g, 0.028 mol) in dry DMF (50 ml). The mixture was stirred overnight. Solvent was removed by evaporation and the residue was partitioned between dichloromethane (100 ml) and 5% aqueous acetic acid (50 ml). On standing HOBT crystallised and was removed by filtration, and the organic layer was separated and washed with aqueous sodium bicarbonate, dried (MgSO4) and evaporated. The residue (8.5 g) was purified by flash chromatography in a sinter funnel eluting with a mixture of dichloromethane and ether (0% to 100% ether). The fractions containing product were combined and evaporated to give Boc-(D)-Met-(L)-Ala-OMe (7.2 g) as a gum which crystallised on standing; NMR (CDCl3): 1.4 (d, 3H), 1.45 (s, 9H), 1.95 (m, 1H), 2.1 (s, 3H), 2.1 (m, 1H), 2.6 (m, 2H), 3.75 (s,3H), 4.3 (bs, 1H), 4.6 (m, 1H), 5.3 (m, 1H), 6.9 (bs, 1H).

Workup

  1. customSolvent was removed by evaporation
  2. customthe residue was partitioned between dichloromethane (100 ml) and 5% aqueous acetic acid (50 ml)
  3. customcrystallised
  4. customwas removed by filtration
  5. customthe organic layer was separated
  6. washwashed with aqueous sodium bicarbonate
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe residue (8.5 g) was purified by flash chromatography in a sinter funnel
  10. washeluting with a mixture of dichloromethane and ether (0% to 100% ether)
  11. additionThe fractions containing product
  12. customevaporated

Sources & evidence

ORD record
ord-c60852020cb743ae95c2e0c6c35ca5f0
Source dataset
uspto-grants-2002_03
Patent number
US06355617B1

Reaction notes

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