4-Methylmorpholine → HCID 18391822, compound

HRID 1611672Notes

Reaction equation

HRID 1611672 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:18]([OH:20])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CN.O.O[N:26]1[C:30]2C=CC=CC=2N=N1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.O>[CH3:30][NH:26][C:18](=[O:20])[C@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]

Participants

9

Reactant 6

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 117439L-Tyrosine, N-(1,1-dimethylethoxy)carbonyl-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 27960291-Hydroxybenzotriazole hydrateHCID 6364545Methylamine hydrochloride

Product 1

HCID 18391822HCID 18391822, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of N-(tert-butoxycarbonyl)-L-tyrosine (300 g, 1.07 mol) in DMF (2 L) were successively added methylamine hydrochloride (86.4 g, 1.28 mol), 1-hydroxybenzotriazole monohydrate (163 g, 1.07 mol, hereinafter to be abbreviated as HOBt.H2O), N-methylmorpholine (258 mL, 2.35 mol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (245 g, 1.28 mol, hereinafter to be abbreviated as WSCI.HCl), under ice-cooling (internal temperature 10° C.). The reaction mixture was stirred for 70 hr while gradually raising the temperature to room temperature. The reaction mixture was poured into iced water (10 L), and the precipitate was collected by filtration and washed with water and ether. The obtained precipitate was recrystallized from ethyl acetate (7 L) to give the title compound (265 g, 84%) as white crystals.

Workup

  1. temperaturewhile gradually raising the temperature to room temperature
  2. filtrationthe precipitate was collected by filtration
  3. washwashed with water and ether
  4. customThe obtained precipitate was recrystallized from ethyl acetate (7 L)

Sources & evidence

ORD record
ord-7f57d569a0934a8fbdaef6c65a97f38a
Source dataset
uspto-grants-2006_01
Patent number
US06989401B2

Reaction notes

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