CHEMBRDG-BB 4002269 synthesis

Yield:845290-58-6 64%

Reaction Conditions:

with lithium aluminium tetrahydride in tetrahydrofuran at 0;Inert atmosphere;Reflux;

Steps:

6

4.6
2-Methyl-2,8-diazaspiro[5.5]undecane (3)
LiAlH₄ in pellets (4.6 g; 121.5 mmol) was stirred vigorously in dry THF (100 mL) under N₂ atmosphere until a suspension of powder was formed (4 h).
This suspension was transferred dropwise via a cannula to the stirred suspension of 11 (5.68 g; 27 mmol) in dry THF (110 mL) under N₂ atmosphere (both suspensions were cooled to 0-5 °C during transfer).
The mixture was then heated in reflux overnight under a N₂ atmosphere, then cooled to 0-5 °C, diluted with THF (50 mL) and the following were slowly added dropwise in 0-5 °C: water (5 mL), 15% aq NaOH (5 mL) and water (15 mL).
The resulting slurry was filtered through Celite, the solids were washed thoroughly with THF (500 mL) and the combined filtrates were concentrated in vacuo to give a brown oil, which was distilled under vacuum (bp 55-60 °C/1.5 mmHg) to give spirodiamine 3 (2.92 g; 64%) as a colourless oil. δ_H (300 MHz, CD₃OD) 2.70-2.40 (4H, m, CH₂NMe, CH₂CH₂CH₂NMe), 2.35-1.85 (4H, m, CH₂NH, CH₂CH₂CH₂NH), 2.10 (3H, s, CH₃), 1.60-1.10 (8H, m, CH₂CH₂CH₂NMe, CH₂CH₂CH₂NMe, CH₂CH₂CH₂NH, CH₂CH₂CH₂NH); δ_C (75.5 MHz, CD₃OD) 65.2 (CH₂NMe), 57.9 (CH₂CH₂CH₂NMe), 55.2 (CH₂NH), 47.6 (CH₂CH₂CH₂NH), 47.2 (CH₃), 35.5 (C 4°), 33.7 (CH₂CH₂CH₂NMe), 30.9 (CH₂CH₂CH₂NH), 22.8 (CH₂CH₂CH₂NH), 22.3 (CH₂CH₂CH₂NMe); m/z (CI) 169 (M+H⁺); HRMS: found: M+H⁺, 169.1697. C₁₀H₂₁N₂ requires 169.1699.

References:

Weinberg, Kamil;Stoit, Axel;Kruse, Chris G.;Haddow, Mairi F.;Gallagher, Timothy [Tetrahedron,2013,vol. 69,# 23,p. 4694 - 4707]