Tetrahydrofuran → HCID 89994505, compound

Participants

Reaction Conditions

Reaction Steps

A flask with thermometer, septum, nitrogen line and stir bar was charged with rac-(7aR,11aS)-11a-(pyridin-2-ylmethyl)-5,6,7,7a,8,10,11,11a-octahydrospiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolane]-3-carb aldehyde (146, R2=Pyridin-2-ylmethyl) (0.5 g, 1.321 mmol) and THF (15 mL). The mixture was cooled to about −5° C. then LiHMDS (1 M in THF) (1.717 mL, 1.717 mmol) was added. The mixture was stirred at about −5° C. for about 30 min then (4-fluorophenyl)magnesium bromide (2 M in Et2O) (1.321 mL, 2.64 mmol) was added. After about 1 h and 15 min water (2 mL) was added and the mixture stirred for about 15 min. The reaction mixture was diluted with EtOAc (25 mL) and water (˜10 mL). The layers were separated then EtOAc (15 mL) and sat. aq. NH4Cl (˜7 mL) were added to the aqueous layer. The layers were separated then the combined organic solutions were dried over Na2SO4, filtered and concentrated under reduced pressure to yield crude rac-(4-fluorophenyl)((7aR,11aS)-11a-(pyridin-2-ylmethyl)-5,6,7,7a,8,10,11,11a-octahydrospiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolan]-3-yl)methanamine (147, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.66 g, 105%) which was used directly in the Step 13 without further manipulation; LC/MS, method 3, Rt=1.67 min, MS m/z 474 (M+H)+.

Provenance & Evidence