METHYL 3-(OXETAN-3-YL)BENZOATE synthesis

Yield:1044507-47-2 27%

Reaction Conditions:

Stage #1: 3-iodooxetane;[3-(methoxycarbonyl)phenyl]boronic acidwith potassium carbonate in 1,4-dioxane at 20 - 27; for 0.333333 h;Inert atmosphere;
Stage #2: with nickel(II) nitrate hexahydrate;4,4'-di-tert-butyl-2,2'-bipyridine in 1,4-dioxane at 80; for 4 h;Inert atmosphere;

Steps:

Step (i)

(3-(Methoxycarbonyl)phenyl)boronic acid (2.0 g, 11.07 mmol), 3-iodooxetane (4.07 g, 22.1 mmol) and K₂CO₃ (4.58 g, 33.2 mmol) were dissolved in dry 1 ,4-dioxane (10 mL). Argon gas was purged through the mixture at room temperature for 20 min, then Ni(NO₃)₂ hexahydrate (0.161 g, 0.55 mmol) and 4,4'-di-tert-butyl-2,2'-dipyridyl (0.14 g, 0.55 mmol) were added and the reaction mixture was heated to 80 °C for 4 hrs. The reaction mixture was then partitioned between water (250 mL) and EtOAc (250 mL). The aqueous layer was further extracted with EtOAc (2 X 150 mL). Organic layers were combined and dried (Na₂SO₄), the solvent was removed in vacuo and the crude product was purified by reverse phase gradient flash column chromatography (reverse phase, C18 silica), product eluted at 0% to 46% ACN in water to afford pure methyl 3-(oxetan-3-yl) benzoate (0.58 g, 27%) as a colourless liquid. 1 H NMR (400 MHz, DMSO-d6) d 3.86 (s, 3H), 4.33 (tt, J = 8.3, 6.6 Hz, 1H), 4.60 (dd, J = 6.6, 6.0 Hz, 2H), 4.97 (dd, J = 8.3, 6.0 Hz, 2H), 7.54 (t, J = 7.7 Hz, 1 H), 7.71 (dt, J = 7.7, 1 .3 Hz, 1 H), 7.87 (dt, J = 7.7, 1 .4 Hz, 1 H), 7.98 (t, J = 1.8 Hz, 1 H).

References:

WO2021/69927,2021,A1 Location in patent:Page/Page column 65-66