Ammonium formate → 1-(3-Fluorophenyl)cyclobutanamine

HRID 260172Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 260172
[F:1][C:2]1[CH:3]=[C:4]([C:8]2([NH:12]C(OCC3C=CC=CC=3)=O)[CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C([O-])=O.[NH4+]>CO.[Pd]>[F:1][C:2]1[CH:3]=[C:4]([C:8]2([NH2:12])[CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Komponenten

5

Edukt 2

HCID 2723923Ammonium formateHCID 86749558HCID 86749558, Verbindung

Produkt 1

HCID 224027501-(3-Fluorophenyl)cyclobutanamineAusbeute 82,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
15 °C

Versuchsvorschrift

A stirred solution of 1-(3-fluorophenyl)cyclobutanecarbamic acid, benzyl ester (8.25 g, 27.6 mmol) and ammonium formate (5.04 g, 79.9 mmol) in methanol (120 mL) under N2 is cooled to 15° C. Ten percent palladium on carbon (1.5 g) is added portionwise over 10 minutes. The reaction mixture is stirred at 15° C. for 45 minutes, then filtered through a small pad of celite. The filter cake is washed with methanol. The filtrate is concentrated. The resulting white solid is partitioned between dichloromethane (150 mL) and saturated aqueous bicarbonate (150 mL). The phases are separated and the aqueous phase extracted with dichloromethane (3×75 mL). The combined organics are washed with saturated aqueous bicarbonate (1×100 mL), water (1×100 mL) and brine (1×100 mL), dried (MgSO4), filtered and concentrated. The organic residue is purified by flash chromatography using 2.5% methanol (saturated with ammonia) in dichloromethane as the eluent to afford 3.77 g of 1-(3-fluorophenyl)cyclobutanamine. This product is the amine used in Step B-2. 1H NMR (CDCl3) δ7.32 (m, 1 H), 7.19 (m, 1 H), 7.09 (m, 1 H), 6.94 (m, 1 H), 2.54 (m, 2 H), 2.12 (m, 3 H), 1.80 (m, 1 H), 1.70 (s, 2 H); 13C NMR (CDCl3) δ164.6, 161.3, 151.99, 151.90, 129.9, 129.8, 120.54, 120.50, 113.3, 113.0, 112.2, 111.9, 58.8, 36.9, 14.1.

Aufarbeitung

  1. filtrationfiltered through a small pad of celite
  2. washThe filter cake is washed with methanol
  3. concentrationThe filtrate is concentrated
  4. customThe resulting white solid is partitioned between dichloromethane (150 mL) and saturated aqueous bicarbonate (150 mL)
  5. customThe phases are separated
  6. extractionthe aqueous phase extracted with dichloromethane (3×75 mL)
  7. washThe combined organics are washed with saturated aqueous bicarbonate (1×100 mL), water (1×100 mL) and brine (1×100 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe organic residue is purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-c757ac45f426480aaedcd0377b161462
Quelldatensatz
uspto-grants-1996_06
Patentnummer
US05525742

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