Reaktion #1137496

Reaktionsgleichung

sodium triacetoxyborohydride

(8R,9aR)-8-[(5-Cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride

4-(Trifluoromethoxy)benzaldehyde

triethylamine

→

title compound

Ausbeute 50.0%

(8R,9aR)-8-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[4-(trifluoromethoxy)benzyl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one

Ausbeute 50.0%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction was stirred at room temperature for an additional four hours
2. 2
   Wascheneluted with ethyl acetate (flow rate=18 mL/minute) over 20 minutes

Vorschrift

(8R,9aR)-8-[(5-Cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride (60 mg, 0.185 mmol, prepared as described in Example 55, Part B) was suspended in dichloromethane (1.0 mL) in a 4-mL scintillation vial. 4-(Trifluoromethoxy)benzaldehyde (45.7 mg, 0.240 mmol, 1.3 equivalents) was added followed by triethylamine (0.051 mL, 0.369 mmol, 2.0 equiv). After stirring for 10 minutes, sodium triacetoxyborohydride (94 mg, 0.443 mmol, 2.4 equivalents) was added, and the reaction was stirred at room temperature for an additional four hours. The suspension was loaded directly onto a 4 g silica gel column and eluted with ethyl acetate (flow rate=18 mL/minute) over 20 minutes to give the title compound as a light yellow oil (42 mg, 50%). 1H NMR (400 MHz, CDCl3) δ ppm 8.03 (d, J=1.2 Hz, 1H), 7.93 (d, J=1.3 Hz, 1H), 7.35 (d, J=8.6 Hz, 2H), 7.17 (d, J=8.0 Hz, 2H), 5.44-5.24 (m, 1H), 4.10 (td, J=9.3, 4.5 Hz, 1H), 3.88 (dd, J=13.2, 5.2 Hz, 1H), 3.74 (dd, J=13.2, 2.0 Hz, 1H), 3.59 (s, 2H), 2.91 (dd, J=12.6, 6.8 Hz, 1H), 2.86-2.71 (m, 2H), 2.71-2.50 (m, 2H), 2.50-2.31 (m, 2H), 2.08-1.82 (m, 2H), 1.00-0.88 (m, 4H); MS (ESI+) m/z 463.1 (M+H)+; [a]D23.6=0.08 (c=0.17, CH3OH).

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