Reaktion #216725

Reaktionsgleichung

2-chloro-4'-fluoroacetophenone

NaI

amine

3-Isopropyl-3,7-diazabicyclo[3.3.1]nonane

→

amine

Ausbeute 86.1%

7-Isopropyl-3-(4-fluorophenacyl)-3,7-diazabicyclo[3.3.1]nonane

Ausbeute 86.1%

Lösungsmittel

H3CCN

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas then heated for 30 minutes with stirrring
2. 2
   Sonstigeto give a light yellow mixture which
3. 3
   FiltrationFiltration (suction)
4. 4
   Sonstigeremoved excess NaI
5. 5
   workup.ADDITIONthe filtrate was diluted with H2O
6. 6
   Sonstigetransferred to a separatory funnel
7. 7
   ExtraktionThe resulting homogenous solution (pH~5) was extracted (ether, 3×75 ml) with the
8. 8
   ExtraktionExtraction (ether, 3×75 ml) of the aqueous layer
9. 9
   Extraktionwas followed by another extraction (H2CCl2, 3×75 ml)
10. 10
    TrocknenThe organic layer (H2CCl2) was dried (Na2SO4, 2 h)
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated
13. 13
    Sonstige(rotary evaporator)

Vorschrift

To a standard setup was added 2-chloro-4'-fluoroacetophenone (7.55 g, 43.8 mmol) and NaI (9.85 g, 65.7 mmol) in H3CCN (30 ml) which was then heated for 30 minutes with stirrring. The solution was allowed to cool to room temperature (30 min) which was followed by dropwise addition of amine 105 (6.7 g, 39.8 mmol) to give a light yellow mixture which was stirred overnight. Filtration (suction) removed excess NaI and the filtrate was diluted with H2O and transferred to a separatory funnel. The resulting homogenous solution (pH~5) was extracted (ether, 3×75 ml) with the latter being discarded, and the pH of the aqueous layer was adjusted to 12 using 10% NaOH. Extraction (ether, 3×75 ml) of the aqueous layer was followed by another extraction (H2CCl2, 3×75 ml) and the ether extracts were discarded. The organic layer (H2CCl2) was dried (Na2SO4, 2 h), filtered, and concentrated (rotary evaporator) to give 2.9 g (86.1%) of amine 55 as a light yellow solid; mp 193°-194° C. IR (KBr) 3060, 3040 (Ar-H), 2940, 2805 (C-H), 1700 (C=O) cm-1 ; 1H NMR (DCCl3) d 1.45 (d, 6 H, CH3 isopropyl), 1.81 [d, 1 H, H(9)ax ], 2.11 [d, 1 H, H(9)eq ], 2.32 lbs, 2 H, H(1,5)], 2.85 (d, 2 H, ring protons), 3.37 (d, 2 H, ring protons), 3.49 (d, 2 H, ring protons), 3.86 (m, 3 H, ring protons, C-H isopropyl), 4.18 (s, 2 H, ArC(O)CH2), 7.15 (t, 2 H, Ar-H), 8.02 (m, 2 H, Ar-H); 13C NMR (DCCl3) ppm 17.01 (CH3 isopropyl), 28.04 [C(1,5)], 30.05 [C(9)], 53.74, 57.2257.34 (ring carbons, C-H isopropyl), 62.22 [ArC(O)CH2 ], 115.58, 115.88, 130.57, 130.70, 131.22, 131.26 (Ar-C), 164.10, 167.49 (J=265.8 Hz, ArC-F), 194.99 (C=O). Ketone 55 was slightly unstable, and thus was reduced to the corresponding alcohol 110.

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