4-Methylmorpholine → Ammonia

HRID 2183035Notes

Reaction equation

HRID 2183035 reaction equation
[CH2:1]([O:8][NH:9][C:10](=[O:32])[CH2:11][C@H:12]([C:22]1[O:23][C:24]([CH3:31])=[C:25]([C:27]([O:29]C)=O)[N:26]=1)[CH2:13][CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.[CH3:44][N:45]1CCOC[CH2:46]1.Cl.CN(C)CCCN=C=NCC.Cl.CNC>ClCCl>[NH3:9].[CH2:1]([O:8][NH:9][C:10](=[O:32])[CH2:11][C@H:12]([C:22]1[O:23][C:24]([CH3:31])=[C:25]([C:27]([N:45]([CH3:46])[CH3:44])=[O:29])[N:26]=1)[CH2:13][CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10473Dimethylamine, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 59909776HCID 59909776, compound

Product 2

HCID 222AmmoniaHCID 59909793HCID 59909793, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl 2-((1R)-1-{2-[(benzyloxy)amino]-2-oxoethyl}-4-cyclohexylbutyl)-5-methyl-1,3-oxazole-4-carboxylate (Preparation 72) (152 mg, 0.36 mmol) in dichloromethane (5 ml) was treated sequentially with 1-hydroxybenzotriazole hydrate (48 mg, 0.36 mmol), N-methylmorpholine (82 μl, 0.75 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (75 mg, 0.39 mmol) and dimethylamine hydrochloride (29 mg, 0.36 mmol) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 17 hours. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate and washed sequentially with water, a saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:0.88 ammonia (95:5:0.5) to afford the title compound as a colourless oil which crystallised on standing (109 mg).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed sequentially with water
  4. dry with materiala saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-958f005774be4575909d21bcd184220f
Source dataset
uspto-grants-2005_05
Patent number
US06897306B2

Reaction notes

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