4-Methylmorpholine → HCID 131732342, Verbindung

HRID 1425703Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1425703
[C:1](N[C@@H](C(O)=O)CO)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=O.C[N:19]1CCOCC1.[CH2:25]([O:29]C(Cl)=O)[CH:26]([CH3:28])[CH3:27].COCC1C=CC(CN)=CC=1>C1COCC1>[CH3:1][O:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:27][CH:26]([CH3:28])[C:25]([NH2:19])=[O:29])=[CH:9][CH:10]=1

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 489184Z-D-Ser-OHHCID 167908271-[4-(Methoxymethyl)phenyl]methanamine

Produkt 1

HCID 131732342HCID 131732342, VerbindungAusbeute 157,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

A THF solution (75 mL) of (R)-Cbz-serine (5.30 g, 22.0 mmol) was stirred and cooled at −78° C. under Ar and then 4-methylmorpholine (NMM) (2.9 mL, 26.4 mmol) was added dropwise. After 2 min of stirring at this temperature, isobutylchloroformate (IBCF) (3.5 mL, 26.4 mmol) was added dropwise leading to the precipitation of a white solid, and the reaction was allowed to proceed for additional 2 min. 4-Methoxymethylbenzylamine (4.00 g, 26.4 mmol) was added portionwise at −78° C. and the mixture was stirred at room temperature (2 h). The white solid was filtered and the organic layer was concentrated in vacuo. The residue was triturated with EtOAc resulting in a solid that was filtered and recrystallized with EtOAc to give (R)-2-N-(benzyloxycarbonyl)amino-3-hydroxy-N-(4-methoxymethy (benzyl) propanamide as a white solid (7.20 g, 88%): Rf=0.63 (EtOAc); mp 138-140° C.; [α]25.8D −34.0° (c 1, DMSO); IR (nujol) 3385, 3294, 3106, 2923, 2859, 1690, 1646, 1544, 1458, 1373, 1307, 1243, 1098, 1028, 919, 738, 694 cm−1; 1H NMR (CDCl3) δ 3.36 (s, OCH3), 3.64 (dd, J=5.1, 10.8 Hz CHH′OH), 3.88-4.06 (br d, CHH′OH), 4.19-4.29 (m, CH), 4.34-4.45 (m, CH2OCH3, NCH2), 5.06 (s, CH2O), 6.96 (d, J=7.2 Hz, OC(O)NH), 7.02-7.14 (br s, NH), 7.19 (d, J=7.8 Hz, 2 ArH), 7.27 (d, J=7.8 Hz, 2 ArH), 7.30-7.38 (m, 5 ArH); 13C NMR (CDCl3) δ 43.2 (NCH2), 55.5 (OCH2CH), 58.1 (CH3O), 62.7 (OCH2CH), 67.3 (CH2O), 74.3 (CH2OCH3), 127.6, 128.0, 128.1, 128.3, 128.5, 135.9, 137.0, 137.5 (8 ArC), 156.7 (OC(O)N), 170.7 (C(O)); HRMS (M+H+)(ESI+) 373.1764 [M+H+] (calcd for C20H24N2O5H+ 373.1763); Anal. Calcd. for C20H24N2O5.0.25H2O: C, 63.73; H, 6.55; N, 7.43. Found: C, 63.35; H, 6.43; N, 7.29.

Aufarbeitung

  1. additionwas added dropwise
  2. customleading to the precipitation of a white solid
  3. filtrationThe white solid was filtered
  4. concentrationthe organic layer was concentrated in vacuo
  5. customThe residue was triturated with EtOAc resulting in a solid
  6. filtrationthat was filtered
  7. customrecrystallized with EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-c379fbbcd92a44e8acc9eb88f505ad6b
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08933065B2

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