4-Methylmorpholine → 2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexylcarbamate

HRID 2246587Notes

Reaction equation

HRID 2246587 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C@H:17]2[CH2:22][CH2:21][C@@H:20]([N:23]([CH:25]([CH3:27])[CH3:26])[CH3:24])[CH2:19][C@H:18]2C(O)=O)[C:13]1=[O:31])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[N:33]1[CH2:38]COCC1.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:46])=CC=1.[CH3:56][Si:57]([CH3:62])([CH3:61])[CH2:58][CH2:59][OH:60]>O1CCOCC1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C@H:17]2[CH2:22][CH2:21][C@@H:20]([N:23]([CH:25]([CH3:27])[CH3:26])[CH3:24])[CH2:19][C@H:18]2[NH:33][C:38](=[O:46])[O:60][CH2:59][CH2:58][Si:57]([CH3:62])([CH3:61])[CH3:56])[C:13]1=[O:31])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 180132-(Trimethylsilyl)ethanolHCID 199401P,P-Diphenylphosphinic azideHCID 24948561(1R,2S,5R)-2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexanecarboxylic acid

Product 1

HCID 685647842-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexylcarbamateYield 49%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A stirring solution of (1R,2S,5R)-2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexanecarboxylic acid (15.0 g, 0.0348 mol) in 1,4-dioxane (200 ml) was charged with N-methylmorpholine (5.26 g, 1.5 eq) and DPPA (14.3 g, 1.5 eq) at 0° C. The mixture was stirred at room temperature for 2 h. The mixture was charged with 2-(trimethylsilyl)ethanol (6.16 g, 1.5 eq) and then stirred for 2.5 h at 85° C. under the protection of nitrogen. The reaction was cooled to room temperature and the solvent was removed under reduced pressure. The resulting residue was dissolved in ethyl acetate (250 ml) and washed with saturated NaHCO3 (3×80 ml) and brine (3×80 ml). The solution was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue obtained was purified with silica gel column chromatography eluting with 1% and 2.5% of methanol in dichloromethane to give 2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexylcarbamate (9.3 g, 49%). LC/MS found [M+H]+=547.

Workup

  1. stirringstirred for 2.5 h at 85° C. under the protection of nitrogen
  2. temperatureThe reaction was cooled to room temperature
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe resulting residue was dissolved in ethyl acetate (250 ml)
  5. washwashed with saturated NaHCO3 (3×80 ml) and brine (3×80 ml)
  6. dry with materialThe solution was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue obtained
  10. customwas purified with silica gel column chromatography
  11. washeluting with 1% and 2.5% of methanol in dichloromethane

Sources & evidence

ORD record
ord-86910226290241ee8eb0efc8e949d610
Source dataset
uspto-grants-2010_03
Patent number
US07687508B2

Reaction notes

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