Reaktion #659234

Reaktionsgleichung

sodium triacetoxyborohydride

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

Triethylamine

4-(trifluoromethoxy)benzaldehyde

→

title compound

Ausbeute 53.0%

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

Ausbeute 53.0%

Lösungsmittel

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added as a neat solid in one portion
2. 2
   Wascheneluted with ethyl acetate (flow rate=18 mL/minute) over 15 minutes

Vorschrift

(8S,9aR)-8-[(5-Cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride (45 mg, 0.139 mmol, prepared as described in Example 46, Part H) was suspended in dichloromethane (1.5 mL) in a 4-mL scintillation vial. Triethylamine (28.0 mg, 0.277 mmol) was added followed by the addition of 4-(trifluoromethoxy)benzaldehyde (34.2 mg, 0.180 mmol) as a solution in dichloromethane (0.2 mL). The resulting solution was stirred at room temperature for 15 minutes, at which point sodium triacetoxyborohydride (70.5 mg, 0.333 mmol) was added as a neat solid in one portion, and the resulting suspension was stirred at room temperature for an additional 4 hours. The suspension was loaded directly onto a 4 g silica column and eluted with ethyl acetate (flow rate=18 mL/minute) over 15 minutes to give the title compound as a colorless oil (34 mg, 53%). 1H NMR (400 MHz, CDCl3) δ ppm 8.02 (d, J=1.2 Hz, 1H), 7.92 (d, J=1.3 Hz, 1H), 7.35 (d, J=8.6 Hz, 2H), 7.17 (d, J=8.0 Hz, 2H), 5.41 (t, J=3.9 Hz, 1H), 4.18 (dd, J=16.4, 9.4 Hz, 1H), 4.02 (dd, J=13.7, 2.0 Hz, 1H), 3.69-3.45 (m, 3H), 2.94 (d, J=12.5 Hz, 2H), 2.81 (d, J=12.0 Hz, 1H), 2.60 (dd, J=14.8, 6.9 Hz, 1H), 2.50-2.34 (m, 2H), 2.15 (dd, J=12.8, 9.3 Hz, 1H), 1.98 (tt, J=7.9, 5.1 Hz, 1H), 1.86 (ddd, J=14.4, 10.4, 4.4 Hz, 1H), 1.02-0.79 (m, 4H); MS (ESI+) m/z 463.1 (M+H)+; [α]D24.1=−0.04 (c=0.23, CH3OH).

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