4-Methylmorpholine → HCID 131721727, compound

HRID 1636332Notes

Reaction equation

HRID 1636332 reaction equation
[NH:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:2]([C:4]([OH:6])=O)[CH3:3].C[N:15]1CCOCC1.ClC(OCC(C)C)=O.[NH:29](N)[C@H:30]([C:35]([N:37]([CH3:40])[O:38][CH3:39])=[O:36])[CH2:31][CH:32]([CH3:34])[CH3:33].Cl>C1COCC1.O1CCOCC1>[CH3:40][N:37]([C:35](=[O:36])[C@H:30]([CH2:31][CH:32]([CH3:33])[CH3:34])[NH:29][C:4](=[O:6])[C@H:2]([CH3:3])[N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[NH2:15])[O:38][CH3:39]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 85082Tert-butoxycarbonylalanineHCID 131721728HCID 131721728, compound

Product 1

HCID 131721727HCID 131721727, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A solution of Boc-Ala-OH (46 mmol) and N-methyl morpholine (46 mmol) in THF (20 ml) was added to a pre cooled solution of isobutyl chloroformate (46 mmol) in THF (30 ml) under nitrogen at between -10 and -15° C. over 30 minutes. The reaction was stirred at -10° C. for 1 hour after which time a solution of N-methyl morpholine (46 mmol) and HCl.H2N-Leu-N(OMe)Me (41.8 mmol) in 1,4-dioxane (20 ml) was added drop wise slowly. The reaction was left for 1 hour at -10° C. and then allowed to warm up to room temperature. After concentrating the solution under high vacuum, water (50 ml) and ethylacetate (200 ml) was added. The organic layer was then washed with 0.1 M citric acid solution (4×50 ml), then saturated sodium bicarbonate (4×50 ml), dried over magnesium sulphate and then concentrated under vacuum to give the product.

Workup

  1. additionwas added drop wise slowly
  2. concentrationAfter concentrating the solution under high vacuum, water (50 ml) and ethylacetate (200 ml)
  3. additionwas added
  4. washThe organic layer was then washed with 0.1 M citric acid solution (4×50 ml)
  5. dry with materialsaturated sodium bicarbonate (4×50 ml), dried over magnesium sulphate
  6. concentrationconcentrated under vacuum
  7. customto give the product

Sources & evidence

ORD record
ord-3303ea0677064961b12c67f049b9a326
Source dataset
uspto-grants-2000_03
Patent number
US06034066

Reaction notes

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