3-Azabicyclo[3.1.0]hexane-6-methanol, 3-(phenylmethyl)- synthesis

Yield:871727-08-1 51%

Reaction Conditions:

Stage #1: 3-benzyl-3-azabicyclo[3.1.0]hexane-2,4-dione-6-carboxylic acid ethyl esterwith lithium aluminium tetrahydride in tetrahydrofuran at 0 - 60; for 36 h;
Stage #2: with water;ammonium chloride in tetrahydrofuran at 0;

Steps:

3

Stage 3 - Reduction; Stage 2 product (37.2g, 136.3mmol) was dissolved in dry THF (40OmL). This solution was added dropwise at 0⁰C to a suspension of LiAIH₄ (20.7g, 545.3mmol) in dry THF (20OmL). The resulting brown suspension was heated to 60⁰C under nitrogen atmosphere for 36h. The mixture was then cooled to 0°C and quenched carefully with saturated NH₄Cl_aq. A grey solid formed and more THF was added to allow adequate stirring. Solid Na₂SO₄ was added to the mixture which was stirred at RT for 30 minutes. The mixture was then filtered through celite to give a pale yellow solution. This was concentrated in vacuo to give the desired product as an orange oil (14.1g, 51%). m/z = 204 [M+H]⁺, ¹H NMR (300MHz, Cf₆- DMSO) δ: 2.25 (2H, d), 2.85 (2H, d), 3.20 (2H, t), 3.55 (2H, s), 4.35 (1 H, t), 7.20-7.40 (5H₁ m).

References:

WO2008/53131,2008,A1 Location in patent:Page/Page column 35; 37