4-Methylmorpholine → HCID 54318947, Verbindung

HRID 963685Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 963685
[Br-].[C:2]1([P+:8]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:9][C:10]#[N:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N([CH2:29][CH3:30])CC)C.[C:31]([O:35][C:36]([NH:38][C@H:39]([C:51](O)=[O:52])[CH:40](CC1C=CC=CC=1)C(O)=O)=[O:37])([CH3:34])([CH3:33])[CH3:32].[CH3:54]N1CCOCC1.[CH2:61]([O:65][C:66](Cl)=[O:67])[CH:62]([CH3:64])[CH3:63].C(C[PH4])#N>C1COCC1>[CH2:61]([O:65][C:66](=[O:67])[CH2:40][CH:39]([NH:38][C:36]([O:35][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:37])[C:51](=[O:52])[C:9]([C:10]#[N:11])=[P:8]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:62]1[CH:64]=[CH:30][CH:29]=[CH:54][CH:63]=1

Komponenten

8

Edukt 6

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 11811037(Cyanomethyl)triphenylphosphonium bromideHCID 14032956HCID 14032956, VerbindungHCID 178511461HCID 178511461, Verbindung

Produkt 1

HCID 54318947HCID 54318947, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a suspension of triphenyl cyanomethyl phosphonium bromide (1, 0.68 g, 1.8 mmol) in anhydrous THF (10 mL) cooled in an ice bath was added triethylamine (396 mg, 546 μL, 3.9 mmol) and the mixture stirred in an ice bath for 15 min. To a solution of N-t-butyloxycarbonyl-β-benzylaspartic acid (2, 575 mg, 1.8 mmol) in THF (15 mL) cooled to -15° C. was added N-methyl morpholine (180 mg, 196 μL, 1.8 mmol) followed by iso-butylchloroformate (243 mg, 231 μL, 1.8 mmol). The resulting solution was stirred at -15° C. for 5 min before being added dropwise with stirring to the previously prepared cyanomethylphosphorane solution. The mixture was stirred at 0° C. for 15 min and then allowed to warm to room temperature and then stirred for a further 16 h. The precipitate was removed by filtration and the solvent removed under reduced pressure. The mixture was purified by chromatography on silica gel (0-50% ethyl acetate in hexane) to yield the product as a clear oil which solidified on drying (0.76 g, 70%): mp 42°-44° C.; 1H NMR (CDCl3) δ1.39 (s, 9H, Boc CH3 's), 2.99 (d, 2H, β--CH2), 5.06 (m, 3H, α--CH & benzyl CH2), 5.62 (d, 1H, NH), 7.28 (m, 5H, benzyl aromatic CH's), 7.52 (m, 15H, PPh3 aromatic CH's); MS (EI, calculated for C36 H35N2O5P, 606.2284) m/e 606.2292 (M+).

Aufarbeitung

  1. temperaturecooled in an ice bath
  2. stirringThe resulting solution was stirred at -15° C. for 5 min
  3. additionbefore being added dropwise
  4. stirringThe mixture was stirred at 0° C. for 15 min
  5. stirringstirred for a further 16 h
  6. customThe precipitate was removed by filtration
  7. customthe solvent removed under reduced pressure
  8. customThe mixture was purified by chromatography on silica gel (0-50% ethyl acetate in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-2e5665cdb28043da96aed536a7efe5c6
Quelldatensatz
uspto-grants-1998_06
Patentnummer
US05763576

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