4-Methylmorpholine → Lysylthreonine

HRID 1006729Notes

Reaction equation

HRID 1006729 reaction equation
N(C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)[C@H:2]([C:4](O)=[O:5])C.O.O[N:26]1[C:30]2[CH:31]=[CH:32][CH:33]=CC=2N=N1.C[N:36]1[CH2:41][CH2:40][O:39]CC1.Cl.C[N:44](C)CCCN=C=NCC.[C:54]([O:57]CC)(=[O:56])[CH3:55]>ClCCl>[CH3:2][C@@H:4]([OH:5])[C@H:55]([NH:44][C:40]([C@@H:41]([NH2:36])[CH2:33][CH2:32][CH2:31][CH2:30][NH2:26])=[O:39])[C:54]([OH:57])=[O:56]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 8857Ethyl AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6364642N-((9H-Fluoren-9-ylmethoxy)carbonyl)-L-alanine

Product 1

HCID 7010718LysylthreonineYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Amine 6 (790 mg, 1.68 mmol) and Fmoc-Ala-OH (578 mg, 1.86 mmol) were dissolved in 40 mL of dry dichloromethane. 1-Hydroxybenzotriazole hydrate (342 mg, 2.53 mmol) was added to this solution, followed by the addition of 4-methylmorpholine (0.30 mL, 2.7 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (391 mg, 2.04 mmol), and the resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate, washed once with saturated aqueous ammonium chloride solution, once with saturated aqueous sodium bicarbonate solution, once with brine, dried (MgSO4), and concentrated. The crude product was purified by flash chromatography on silica gel, eluting with 40% ethyl acetate-hexanes, to give 1.17 g (91%) of 7 as a white solid. 1H-NMR (300 MHz, CDCl3): d 7.76 (d, J=7 Hz, 2H), 7.62-7.55 (m, 2H), 7.40 (t, J=7 Hz, 2H), 7.35-7.28 (m, 7H), 6.95-6.46 (m, 2H), 5.45-5.25 (m, 1H), 5.11-5.05 (m, 2H), 4,75-4.30 (m, 5H), 4.28-4.04 (m, 4H), 3.94-3.76 (m, 1H), 3.50-3.36 (m, 1H), 2.95-2.61 (m, 2H), 1.82-1.65 (m, 2H), 1.54-1.41 (m, 4H), 1.39-1.32 (m, 3H).

Workup

  1. washwashed once with saturated aqueous ammonium chloride solution, once with saturated aqueous sodium bicarbonate solution, once with brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography on silica gel
  5. washeluting with 40% ethyl acetate-hexanes

Sources & evidence

ORD record
ord-89516119c5ee4a1b8255400dc49c95b6
Source dataset
uspto-grants-2004_09
Patent number
US06790989B2

Reaction notes

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