Sodium hydride → 4-((3-Fluorobenzyloxy)methyl)benzonitrile

HRID 73147

Reaktionsgleichung

Reaktionsgleichung von HRID 73147
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].[H-].[Na+].[C:12]([C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Br)=[CH:16][CH:15]=1)#[N:13].[NH4+].[Cl-]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][O:6][CH2:18][C:17]1[CH:20]=[CH:21][C:14]([C:12]#[N:13])=[CH:15][CH:16]=1

Komponenten

6

Edukt 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 680083-Fluorobenzylic alcoholHCID 869964-(Bromomethyl)benzonitrile

Produkt 1

HCID 462235894-((3-Fluorobenzyloxy)methyl)benzonitrileAusbeute 81,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

3-(Fluoro)benzylalcohol (5.00 g, 39.6 mmol) in THF (50 mL) was added dropwise at 0° C. to a THF (100 mL) suspension of NaH (60%, 6.3 g, 158.4 mmol). The mixture was stirred at 0° C. (30 min). Then, a THF solution of 4-cyanobenzylbromide (9.30 g, 47.6 mmol) was added dropwise at 0° C. and the mixture was stirred at room temperature (16 h). A saturated aqueous solution of NH4Cl (40 mL) was added dropwise at 0° C. and the layers were separated. The aqueous layer was washed with CH2Cl2 (60 mL). The organics layers were combined, dried (Na2SO4) and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with EtOAc/hexanes (0/10 to 1/9) as the eluant to obtain 4-((3-fluorobenzyloxy)methyl)benzonitrile as a colorless oil (7.80 g, 81%): Rf 0.65 (hexanes/EtOAc 8/2); IR (nujol) 2863, 2229, 1719, 1595, 1451, 1450, 1360, 1258, 1100, 1018, 945, 862, 790, 687, 554 cm−1; 1H NMR (CDCl3) δ 4.59 (s, CH2O), 4.61 (s, CH2O), 6.97-7.14 (m, 3 ArH), 7.26-7.37 (m, 1 ArH), 7.47 (d, J=7.5 Hz, 2 ArH), 7.65 (d, J=7.5 Hz, 2 ArH); 13C NMR (CDCl3) δ 71.2 (CH2O), 71.9 (CH2O), 113.4 (CCN), 114.4 (d, J=21.6 Hz, C2′ or C4′), 114.7 (d, J=21.6 Hz, C4′ or C2′), 118.8 (CN), 122.9 (d, J=2.3 Hz, C6′), 127.7 (ArC), 130.0 (d, J=9.2 Hz, C6′), 132.2 (ArC), 140.2 (d, J=8.0 Hz, C1′), 143.5 (ArC), 162.9 (d, J=244.8 Hz, C3′); HRMS (M+Cs+) (ESI+) 373.9957 [M+Cs+] (calcd for C15H12FNOCs+373.9954); Anal. Calcd. for C15H12FNO2: C, 74.67; H, 5.01; F, 7.87; N, 5.81. Found: C, 74.53; H, 4.93; F, 7.75; N, 5.81.

Aufarbeitung

  1. stirringthe mixture was stirred at room temperature (16 h)
  2. customthe layers were separated
  3. washThe aqueous layer was washed with CH2Cl2 (60 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by flash column chromatography on silica gel with EtOAc/hexanes (0/10 to 1/9) as the eluant

Quellen und Nachweise

ORD-Eintrag
ord-92665c8e40c44534a894241ca85b70aa
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829033B2

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