Acetic Acid → 4-{4-[(1-cyclobutylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrile

HRID 273061Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 273061
[NH:1]1[CH2:4][CH:3]([CH2:5][O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3([C:19]#[N:20])[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:9][CH:8]=2)[CH2:2]1.[C:21]1(=O)[CH2:24][CH2:23][CH2:22]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.C(=O)([O-])[O-].[Na+].[Na+]>[CH:21]1([N:1]2[CH2:4][CH:3]([CH2:5][O:6][C:7]3[CH:8]=[CH:9][C:10]([C:13]4([C:19]#[N:20])[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)=[CH:11][CH:12]=3)[CH2:2]2)[CH2:24][CH2:23][CH2:22]1

Komponenten

7

Edukt 4

HCID 176Acetic AcidHCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 68576445HCID 68576445, Verbindung

Produkt 1

HCID 598374294-{4-[(1-cyclobutylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrileAusbeute 81,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 10340Sodium CarbonateLösungsmittel

Versuchsvorschrift

4-[4-(azetidin-3-ylmethoxy)phenyl]tetrahydro-2H-pyran-4-carbonitrile (0.29, 0.73 mmol) was dissolved in THF (2 mL). Cyclobutanone (0.06 mL, 0.80 mmol) and acetic acid (0.042 mL, 0.73 mmol) were added. The mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (0.311 g, 1.47 mmol) was added. The mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with 10% aqueous sodium carbonate (5 mL) then extracted with DCM (2×50 mL). The organics were combined, dried over sodium sulphate, filtered and concentrated in vacuo to provide a clear oil. This was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 95:5:0.5) to provide the title compound (0.194 g, 81%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 1.60-1.70 (m, 2H), 1.70-1.80 (m, 2H), 1.80-1.90 (m, 2H), 1.95-2.00 (m, 2H), 2.0-2.15 (m, 2H), 2.9 (m, 1H), 3.1 (t, 2H), 3.16 (m, 1H), 3.4 (t, 2H), 3.9 (m, 2H), 4.10 (m, 4H), 6.90 (d, 2H), 7.40 (d, 2H). HRMS ESI+ m/z 327.2059 [MH]+.

Aufarbeitung

  1. stirringThe mixture was stirred at room temperature for 18 hours
  2. extractionthen extracted with DCM (2×50 mL)
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a clear oil
  7. customThis was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 95:5:0.5)

Quellen und Nachweise

ORD-Eintrag
ord-f8a3de240ae94ccca137dea9a70939fd
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07456164B2

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