4-Methylmorpholine → HCID 15481806, compound

HRID 887947Notes

Reaction equation

HRID 887947 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][C@H:10]([C@@H:14]([N:16]([CH:24]=[O:25])[O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[CH3:15])[C:11]([OH:13])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[CH3:70][NH:71][C:72](=[O:79])[C@@H:73]([NH2:78])[C:74]([CH3:77])([CH3:76])[CH3:75]>CN(C=O)C>[CH3:75][C:74]([CH3:77])([CH3:76])[C@H:73]([NH:78][C:11](=[O:13])[C@H:10]([CH2:9][CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C@@H:14]([N:16]([CH:24]=[O:25])[O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[CH3:15])[C:72](=[O:79])[NH:71][CH3:70]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 445856(2S)-2-Amino-N,3,3-trimethylbutanamideHCID 11245009HCID 11245009, compound

Product 1

HCID 15481806HCID 15481806, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2R,3S)-2-(3-phenyl-1-propyl)-3-(formyl-2-tetrahydropyranyloxyamino)buta noic acid (5.5 g, 15.76 mmol) in DMF (20 mL) is added BOP reagent (7.66 g, 17.34 mmol), HOBt (2.34 g, 17.34 mmol), and NMM (4.78 g, 47.28 mmol). After 30 min, addition of (2S)-2-Amino-3,3-dimethylbutanoic acid methylamide (3.4 g, 23.64) occurs and the resulting solution is stirred at 25.degree. C. for 20 h. The reaction mixture is poured into ethyl acetate/hexanes (1:1, 200 mL) and washed sequentially with 1 M hydrochloric acid, 1 M aqueous sodium carbonate, and saturated aqueous sodium chloride. The organic layer is dried over magnesium sulfate, concentrated in vacuo, and purified by silica gel chromatography (elution with 2:1 ethyl acetate-hexane) to provide (2R,3S)-3-(Formyl-2-tetrahydropyranyloxyamino)-2-(3-phenyl-1-propyl)butanoic acid [(1S)-2,2-dimethyl-1-(methylcarbamoyl)-1-propyl]amide as a white solid (2.7 g, 36% yield).

Workup

  1. waitfor 20 h
  2. washwashed sequentially with 1 M hydrochloric acid, 1 M aqueous sodium carbonate, and saturated aqueous sodium chloride
  3. dry with materialThe organic layer is dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified by silica gel chromatography (elution with 2:1 ethyl acetate-hexane)

Sources & evidence

ORD record
ord-8238f65127384d59aaf113dbc7225e74
Source dataset
uspto-grants-2012_08
Patent number
US08247451B2

Reaction notes

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