Glycosmicine → (2r)-t-Butoxycarbonylamino-5-(1,2,3,4-tetrahydro-1-methyl-2,4-dioxoquinazolin-3-yl)pentanoic acid t-butyl ester

HRID 651339

Reaktionsgleichung

Reaktionsgleichung von HRID 651339
[H-].[Na+].[CH3:3][N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7](=[O:14])[NH:6][C:5]1=[O:15].[C:16]([O:20][C:21](=[O:35])[C@H:22]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][CH2:24][CH2:25]I)([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C.C1OCCOCCOCCOCCOCCOC1>[C:16]([O:20][C:21](=[O:35])[C@H:22]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][CH2:24][CH2:25][N:6]1[C:7](=[O:14])[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:4]([CH3:3])[C:5]1=[O:15])([CH3:17])([CH3:18])[CH3:19]

Komponenten

6

Edukt 3

HCID 11788GlycosmicineHCID 24758Sodium hydrideHCID 15479355N-Boc-5-Iodo-D-norvaline tert-butyl ester

Produkt 1

HCID 69288498(2r)-t-Butoxycarbonylamino-5-(1,2,3,4-tetrahydro-1-methyl-2,4-dioxoquinazolin-3-yl)pentanoic acid t-butyl esterAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 2855718-Crown-6KatalysatorHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

Sodium hydride (0.408 g, 10.2 mmol) was added to a solution of 1,2,3,4-tetrahydro-1-methyl-2,4-dioxoquinazoline (2.17 g, 12.4 mmol) and 18-crown-6 (0.045 g) in 25 mL of DMF. After stirring at RT for 30 min, (2R)-(t-butyloxycarbonylamino)-5-iodopentanoic acid t-butyl ester (3.60 g, 9.02 mmol) in 15 mL of DMF was added, and the solution was stirred at RT for 30 min, then at 60° C. for 6 h. The solvent was removed under reduced pressure, and the residue was partitioned between ethyl acetate and 0.05M aqueous HCl. The organic phase was washed with water and brine, dried over MgSO4 and concentrated. The crude material was purified by silica gel chromatography (hexane/ethyl acetate 3/1˜2/1) to give the title compound (3.81 g, 95% yield): NMR (400 MHz, CDCl3) 1.42 (s, 9H), 1.45 (s, 9H), 1.60-1.88 (m, 4H), 3.60 (s, 3H), 4.08-4.21 (m, 3H), 5.06 (br d, 1H, J=8.1 Hz), 7.19-7.31 (m, 2H), 7.68 (dt, 1H, J=7.84, 1.56 Hz), 8.22 (dd, 1H, J=7.88, 1.52 Hz).

Aufarbeitung

  1. stirringthe solution was stirred at RT for 30 min
  2. waitat 60° C. for 6 h
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was partitioned between ethyl acetate and 0.05M aqueous HCl
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude material was purified by silica gel chromatography (hexane/ethyl acetate 3/1˜2/1)

Quellen und Nachweise

ORD-Eintrag
ord-a47daa744a794d46a8a7db35e54db661
Quelldatensatz
uspto-grants-2001_08
Patentnummer
US06277987B1

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