1,8-Diazabicyclo(5.4.0)undec-7-ene → Racemic (7S*,9aS*)-2-(Benzo[d]isoxazol-3-yl)perhydro-7-(hydroxymethyl)-1H-pyrido[1,2-a]pyrazine

Participants

Reaction Conditions

Reaction Steps

A mixture consisting of racemic (7S*,9aS*)-7-(hydroxymethyl)perhydro-1H-pyrido[1,2-a]pyrazine (see Example 27; 500 mg, 2.93 mmol), 3-chloro-1,2-benzisoxazole (890 mg, 5.86 mmol) and 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU, 446 mg, 0.438 ml, 2.93 mmol) in 2,6-lutidine (0.5 ml) was stirred and heated at 145° C. for 18 hours. The solvent was removed in vacuo, and the tarry residue was thoroughly extracted with methylene chloride (150 ml). Insolubles were filtered and the solvent was removed in vacuo to afford a dark brown residue. Flash chromatography of the entire sample (20 g silica gel, 32-63 mesh; eluting with ethyl acetate/methanol=95:5 in volume) afforded 350 mg (41.7%) of the title compound (in which the 7- and 9a-hydrogen substituents remain cis) as a colorless amorphous solid. HRMS m/z 287.1639 (M, C16H21N3O2). 13CNMR (CDCl3) delta 164.0, 161.0, 129.5, 122.3, 122.1, 116.1, 110.5, 67.5, 60.2, 58.2, 54.2, 53.7, 48.3, 34.4, 26.9, 26.3.

Provenance & Evidence