(1R,2R)-2-Aminocyclohexanol → 3-(3,5-Difluorophenyl)oxetane

HRID 705213

Reaktionsgleichung

Reaktionsgleichung von HRID 705213
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[C:6]([F:8])[CH:7]=1.N[C@@H]1CC[CH2:16][CH2:15][C@H:14]1[OH:19].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].IC1COC1>CC(O)C.[Ni](I)I>[F:1][C:2]1[CH:3]=[C:4]([CH:15]2[CH2:14][O:19][CH2:16]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Komponenten

7

Edukt 4

HCID 735777(1R,2R)-2-AminocyclohexanolHCID 2724254Sodium bis(trimethylsilyl)amideHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 133566863-Iodooxetane

Produkt 1

HCID 706553403-(3,5-Difluorophenyl)oxetaneAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 26038Nickel(II) iodideKatalysatorHCID 3776IsopropanolLösungsmittel2×

Versuchsvorschrift

3,5-difluorophenylboronic acid (2.0 equiv.), (1R,2R)-2-aminocyclohexanol (0.06 equiv.), NaHMDS (2.0 equiv.), and nickel(II) iodide (0.06 equiv.) were dissolved in 2-propanol (0.35 M). The mixture was degassed with N2, stirred at rt for 10 min and then a solution of 3-iodooxetane (1.0 equiv.) in 2-Propanol (0.70 M) was added. The mixture was sealed and heated at 80° C. in the microwave for 20 min. The mixture was filtered through celite, eluting with EtOH and concentrated. The crude residue was purified by ISCO SiO2 chromatography eluting with 0-100% EtOAc in Heptanes to afford 3-(3,5-difluorophenyl)oxetane in 63% yield. 1H NMR (400 MHz, <cdcl3>) δ 6.88-6.96 (m, 2H), 6.72 (tt, J=2.20, 8.95 Hz, 1H), 5.08 (dd, J=6.26, 8.22 Hz, 2H), 4.71 (t, J=6.26 Hz, 2H), 4.14-4.24 (m, 1H).

Aufarbeitung

  1. customThe mixture was degassed with N2
  2. customThe mixture was sealed
  3. temperatureheated at 80° C. in the microwave for 20 min
  4. filtrationThe mixture was filtered through celite
  5. washeluting with EtOH
  6. concentrationconcentrated
  7. customThe crude residue was purified by ISCO SiO2 chromatography
  8. washeluting with 0-100% EtOAc in Heptanes

Quellen und Nachweise

ORD-Eintrag
ord-43df638c606d45588962237d0b98474b
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09173883B2

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