Lithium Hexamethyldisilazide → (4R)-2-oxo-N-[(1R)-1-phenylpropyl]-4-(pyrimidin-2-ylsulfanylmethyl)azetidine-1-carboxamide

HRID 321941Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 321941
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[S:7][CH2:8][C@@H:9]1[NH:12][C:11](=[O:13])[CH2:10]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:24]1([C@H:30]([N:33]=[C:34]=[O:35])[CH2:31][CH3:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1>[C:24]1([C@H:30]([NH:33][C:34]([N:12]2[C@@H:9]([CH2:8][S:7][C:2]3[N:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[CH2:10][C:11]2=[O:13])=[O:35])[CH2:31][CH3:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Komponenten

5

Edukt 3

HCID 2733832Lithium HexamethyldisilazideHCID 7018288(R)-(+)-1-Phenylpropyl isocyanateHCID 543962814(R)-(pyrimidin-2-ylsulfanylmethyl)azetidin-2-one

Produkt 1

HCID 479658(4R)-2-oxo-N-[(1R)-1-phenylpropyl]-4-(pyrimidin-2-ylsulfanylmethyl)azetidine-1-carboxamideAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 4(R)-(pyrimidin-2-ylsulfanyl-methyl)azetidin-2-one (61.5 mg, 0.315 mmol) in THF (3 mL) at 0° was added dropwise LiHMDS (1M/THF) (0.33 mL, 0.331 mmol). After the reaction mixture was stirred 15 min at 0°, then cooled to −78°, 1(R)-phenylpropyl isocyanate (example 1) (0.53M/toluene, 0.63 mL, 0.315 mmol) was added dropwise and the mixture was warmed to room temperature and stirred for 1.5 h. The reaction mixture was quenched with H2O and diluted with EtOAc. The organic phase was washed with H2O and brine, dried (MgSO4), filtered and evaporated. The product was purified by flash chromatography (SiO2, 30% EtOAc/hexane) to give 2-oxo-4(R)-(pyrimidin-2-ylsulfanylmethyl)azetidine-1-carboxylic acid (1(R)-phenylpropyl)amide (75 mg, 67% yield) as a viscous gum. 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J=4.8 Hz, 2H), 7.29-7.17 (m, 5H), 6.94 (t, J=4.8 Hz, 1H), 6.82 (d, J=8.3 Hz, 1H) 4.71 (q, J=7.6 Hz, 1H), 4.33-4.28 (m, 1H), 4.03 (dd, J=14.2, 3.3 Hz, 1H), 3.39 (dd, J=14.2, 8.3 Hz, 1H), 3.03 (dd, J=16.0, 5.6 Hz, 1H), 2.89 (dd, J=16.0, 3.0 Hz, 1H), 1.83-1.75 (m, 2H), 0.86 (t, J=7.3 Hz, 3H); IR (neat) υ 1758, 1692 cm−1; FAB MS m/z 357.3 (MH+); HRMS calcd. for C18H21N4O2S (MH+) 357.1385, found 357.1379.

Aufarbeitung

  1. temperaturecooled to −78°
  2. stirringstirred for 1.5 h
  3. customThe reaction mixture was quenched with H2O
  4. additiondiluted with EtOAc
  5. washThe organic phase was washed with H2O and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe product was purified by flash chromatography (SiO2, 30% EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-342bc74d26cd4e2f9a704bedb14a9ea4
Quelldatensatz
uspto-grants-2001_04
Patentnummer
US06211170B1

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