Ethyl 1-bromocyclobutanecarboxylate

Clear colorless liquid

To a 20-L 4-necked round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed LDA solution in THF (1 M) (2295 mL, 1.10 equiv) followed by the addition of a solution of ethyl cyclobutanecarboxylate (500 g, 3.90 mol, 1.00 equiv) in tetrahydrofuran (2.5 L) dropwise with stirring at -78°C. The mixture was stirred at -60°C for 1 h. To this was added a solution of tetrabromomethane (1250 g, 3.77 mol, 1.00 equiv) in tetrahydrofuran (1250 mL) dropwise with stirring. The resulting solution was stirred overnight from -70°C to room temperature, quenched by the addition of 600 mL of saturated aqueous NHN-Bromosuccinimide (17.2 g, 96.6 mmol) and AIBN (1.28 g, 7.8 mmol) were added sequentially to a solution of ethyl cyclobutanecarboxylate (10.0 g, 78.0 mmol) in CC14 (140 mL) at 25°C. The reaction mixture was heated to 80°C and was maintained at that temperature for 16h whereupon TLC analysis showed that the desired product was formed (3percent EtOAc in petroleum ether, Rf = 0.4). The mixture was cooled to room temperature then was diluted with DCM (100 mL) and washed with water (100 mL x 2) and brine (100 mL). The organic layer was dried over Na2SO4, filtered, and was concentrated. The residue was purified by flash column chromatography (1-3percent EtOAc in petroleum ether) to afford compound A16 (6.4 g, 40percent) as colorless oil, which was used without additional characterization.Description 62Ethyl 1-bromocyclo butanecarboxylate (D62)To a solution of ethyl cyclobutanecarboxylate (10 g) in Cd4 (100 mL) was added NBS (20.83 g)and AIBN (1.281 g). The mixture was stirred at 80°C for 2 hours. Water (50 mL) was added andthe mixture was extracted with EtOAc (3 x50 mL). The combined organic was washed with saturated NaHCO3 (50 mL), water (50 mL) and brine (50 mL), dried over MgSO4 and evaporated. The residue was purified by column chromatography (silica gel, petroleum ether/EtOAc = 100:1) to afford the title compound (10 g) as yellow oil. ‘H NMR (400 MHz, CDC13): 4.26 (q, J 14.4, 7.2Hz, 2H), 2.95-2.88 (m, 2H), 2.67-2.59 (m, 2H), 2.26-2.21 (m, 1H), 1.91-1.86 (m, 1H), 1.32 (t, J=7.2 Hz, 3H).A) Ethyl 1-azidocyclobutane-1 -carboxylate: To a flask was added General procedure: (0564) Bromodecarboxylation of alkanoic acids (0565) bromoisocyanurate (0566) RC02H -1 · RBr (0567) hv (0568) [00169] A mixture of alkanoic acid RC02H (2 mmol), bromoisocyanurate, additive (optionally) and solvent (12 mL) was stirred under fluorescent room light irradiation (FL). The reaction mixture washed with 1 M aq Na2S03, dried over Na2S04, filtered through short silica gel pad and concentrated in vacuo to yield crude alkyl bromide RBr. Optionally, the crude bromide was purified by chromatography on silica gel. The results are presented in Table 11.PREPARATION 21 1-Bromo-1-ethoxycarbonylcyclobutane 63.2% Yield, used without further purification.

Molecular Weight:207.06
XLogP3:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:205.99424
Monoisotopic Mass:205.99424
Topological Polar Surface Area:26.3
Heavy Atom Count:10
Complexity:141
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes