4-Methylmorpholine → HCID 69019295, compound

HRID 133839Notes

Reaction equation

HRID 133839 reaction equation
[CH3:1][C@@H:2]([C:6]([CH3:14])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:7])[C:3]([OH:5])=O.OC1C2N=NNC=2C=CC=1.CN1CCOCC1.Cl.[CH3:33]/[C:34](=[CH:40]\[C@@H:41]([N:45]([CH3:54])[C:46](=[O:53])[C@H:47]([C:49]([CH3:52])([CH3:51])[CH3:50])[NH2:48])[CH:42]([CH3:44])[CH3:43])/[C:35]([O:37][CH2:38][CH3:39])=[O:36]>CN(C)C=O>[CH3:1][C@@H:2]([C:6]([CH3:14])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:7])[C:3]([NH:48][C@@H:47]([C:49]([CH3:52])([CH3:50])[CH3:51])[C:46]([N:45]([CH3:54])[C@@H:41]([CH:42]([CH3:43])[CH3:44])/[CH:40]=[C:34](\[CH3:33])/[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:53])=[O:5]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 11183134HCID 11183134, compoundHCID 86593101610786-70-4HCID 178418300HCID 178418300, compound

Product 1

HCID 69019295HCID 69019295, compoundYield 73.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C., ice bath) solution of (2S)-2,3-dimethyl-3-phenylbutanoic acid (0.11 g, 0.57 mmol, from Reference Example 25), hydroxybenzotriazole (93 mg, 0.69 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimine hydrochloride (0.15 g, 0.80 mmol) in anhydous dimethylformamide (2 ml) is added N-methylmorpholine (95 uL, 0.86 mmol) via syringe under an inert atmosphere. After stirring for 15 minutes at 0° C., the cooling bath is removed, and the resulting mixture is stirred for 1 hour. The solution is cooled at 0° C. (ice water bath), and to this mixture is added a solution of ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate hydrochloride (0.56 mmol) in anhydrous dimethylformamide (2 ml). The cooling bath is removed, and the resulting mixture is stirred for 22 hours at room temperature under an inert atmosphere. The mixture is diluted with water, and the aqueous layer is extracted with ethyl acetate (3 times). The combined extracts are washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue is chromatographed (silica gel, flash column), to provide a white foam (0.20 g, 71%). MS (ES+): (M+H)=487.0

Workup

  1. customthe cooling bath is removed
  2. stirringthe resulting mixture is stirred for 1 hour
  3. temperatureThe solution is cooled at 0° C. (ice water bath)
  4. customThe cooling bath is removed
  5. stirringthe resulting mixture is stirred for 22 hours at room temperature under an inert atmosphere
  6. additionThe mixture is diluted with water
  7. extractionthe aqueous layer is extracted with ethyl acetate (3 times)
  8. washThe combined extracts are washed with saturated aqueous sodium chloride
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue is chromatographed (silica gel, flash column)

Sources & evidence

ORD record
ord-64c8a97858744600b952717dfb0e3d26
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Reaction notes

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