1-boc-3-(1h-iMidazol-2-yl)azetidine synthesis

Yield:1234710-02-1 42%

Reaction Conditions:

with ammonia at 0 - 26; for 14.1667 h;

Steps:

95.1 Step 1: Preparation of tert-butyl 3-(1H-imidazol-2-yl)azetidine-1-carboxylate

Step 1:
Preparation of tert-butyl 3-(1H-imidazol-2-yl)azetidine-1-carboxylate
Ammonia gas was bubbled through a mixture of tert-butyl 3-formylazetidine-1-carboxylate (1.0 g, 5.4 mmol, 1.0 eq) and glyoxal (10.9 g, 40 wt % in water, 75.59 mmol, 14 eq.) at 0° C. for 10 min, until the weight of the solution increase 1.84 g (about 107.98 mmol of NH₃).
The mixture was allowed to warm to 26° C. and stirred for 14 hours.
The aqueous layers were extracted with CH₂Cl₂.
The combined organic phase was dried over Na₂SO₄, filtered and concentrated under reduced pressure.
The residue was purified by silica gel chromatography eluting with 70% EtOAc in hexane to afford the title compound (0.51 g, 42% yield) as a light yellow solid. MS (ESI) m/z 224.0 [M+H]⁺.
¹H NMR (400 MHz, CDCl₃) δ 7.01 (s, 2H), 4.28 (t, J=8.8 Hz, 2H), 4.16-4.11 (m, 2H), 3.88-3.86 (m, 1H), 1.44 (s, 9H).

References:

US2018/271837,2018,A1 Location in patent:Paragraph 0334-0335