4-Cyanobenzaldehyde → tert-Butyl 1-(4-cyanobenzyl)azetidine-3-carboxylate

HRID 1804439Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1804439
C(O)(=O)C.[NH:5]1[CH2:8][CH:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6]1.[CH:16]([C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1)=O.C([BH3-])#N.[Na+]>CO>[C:22]([C:21]1[CH:24]=[CH:25][C:18]([CH2:16][N:5]2[CH2:6][CH:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8]2)=[CH:19][CH:20]=1)#[N:23]

Komponenten

5

Edukt 3

HCID 660424-CyanobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 66677484tert-Butyl azetidine-3-carboxylate acetate

Produkt 1

HCID 58504367tert-Butyl 1-(4-cyanobenzyl)azetidine-3-carboxylateAusbeute 89 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of tert-butyl azetidine-3-carboxylate acetic acid salt (92.0 g, 0.423 mol) in methanol (1.0 L) at room temperature was added 4-formylbenzonitrile (50.8 g, 0.381 mol). The reaction mixture was cooled to 0° C., and sodium cyanoborohydride (28.8 g, 0.458 mol) was added portion-wise. The reaction mixture was allowed to warm to room temperature and stirring continued overnight. After the reaction mixture was concentrated under reduced pressure the residue was diluted with 10% aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was collected, washed with brine, and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by silica gel chromatography using 20% ethyl acetate in petroleum ether afforded tert-butyl 1-(4-cyanobenzyl)azetidine-3-carboxylate (89%) (After chromatography, Int.1-D contained a small amount of 4-hydroxymethylbenzonitrile. This material was taken forward to the next step without further purification). LC/MS M+1=273.18. 1H NMR (400 MHz, CDCl3) δ ppm 1.46 (s, 9H), 3.22-3.31 (m, 3H), 3.48-3.56 (m, 2H), 3.66 (s, 2H), 7.39 (d, J=8.28 Hz, 2H), and 7.60 (d, J=8.28 Hz, 2H).

Aufarbeitung

  1. temperatureto warm to room temperature
  2. concentrationAfter the reaction mixture was concentrated under reduced pressure the residue
  3. additionwas diluted with 10% aqueous sodium bicarbonate solution
  4. extractionextracted with ethyl acetate
  5. customThe organic layer was collected
  6. washwashed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationConcentration under reduced pressure
  9. customfollowed by purification by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-d483d56491564a01aecc1d3e3a0da7f5
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354398B2

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