3-FORMYL-AZETIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER

To a stirringsolutionof tert-butyl 3-(hydroxymethyl)azetidine-1-carboxylate(20.96 g, 112 mmol) in EA (500 ml)was added IBX (62.69 g, 224 mmol) and the reaction was refluxed overnight. The reaction was cooledto rt, PE (500 ml)was added and the reaction mixture was filtered. The filtrate was concentrated under reduced pressureto give compound1.3 as yellow oil product (20.56 g, 99percent). 1H NMR (400 MHz, CDCI3) i5 1.44 (s, 9 H), 3.32-3.4015 (m, 1 H), 4.07-4.14 (m, 4 H), 9.85 (d, J = 2.0Hz, 3 H).Dimethyl sulfoxide (1.1 mL, 15.0 mmol) was slowly added to 20 mL of oxalyl chloride (1.3 mL, 15.0 mmol) dissolved in distilled methylene chloride solution at -78° C., and the mixture was stirred at the same temperature for 30 minutes. [0045] Dimethyl sulfoxide (1.1 mL, 15.0 mmol) was slowly added to 20 mL of oxalyl chloride (1.3 mL, 15.0 mmol) dissolved in distilled methylene chloride solution at -78°C, and the mixture was stirred at the same temperature for 30 minutes. Then, tertiary butyl 3-(hydroxymethyl)azetidine-1-carboxylate (900 mg, 5.0 mmol) was added thereto, and the mixture was stirred at the same temperature for 3 hours. Thereafter, triethylamine (6.0 mL, 45.0 mmol) was slowly added at -78°C, and the mixture was stirred for 1 hour. The reaction mixture was extracted with methylene chloride (3*30 mL), and the organic layer was washed with a saturated sodium chloride solution and distilled water once, respectively and dried over anhydrous magnesium sulfate. The solvent was removed by reduced pressure evaporation to obtain a light yellow liquid, which was purified by flash chromatography (n-hexane: ethyl acetate (1:1, v/v)). The product was identified as a single compound by TLC (thin layer chromatography); n-hexane: ethyl acetate (1:1, v/v)). Yield: 85percent, yellow oily liquid To a solution of oxalyl chloride (0.112 mL, 1.282 mmol) in DCM (4 mL) at -78 °C under Ar was added DMSO (0.182 mL, 2.56 mmol) dropwise. The mixture was stirred at -78 °C for 30 min and a solution of fert-butyl 3-(hydroxymethyl)azetidine-l-carboxylate (200 mg, 1.068 mmol) in DCM (1 mL) was added. The mixture was stirred at -78 °C for 30 min and added TEA (0.744 mL, 5.34 mmol). The reaction was allowed to warm up to room temperature and stirred for 30 min. The mixture was cooled to 0 °C and quenched with 1 N HCl. The mixture was warmed to room temperature and extracted with DCM. The organic layer was washed with brine, dried over MgSCn, filtered and concentrated. The residue was purified by flash chromatography (0-50percent EtOAc:hexanes) to yield E6A (148 mg, 75percent). NMR (500 MHz, CDCh) δ 9.86 (d, J = 2.20 Hz, 1H), 4.04-4.17 (m, 4H), 3.32-3.40 (m, 1H), 1.45 (s, 9H).To a stirred solution of oxalyl chloride (4.28 niL, 4.98 mmol) in DCM (5 niL) at -78 °C is added DMSO (0.71 mL, 9.96 mL) dropwise. After stirring for 15 mins tert-butyl 3- (hydroxymethyl)azetidine-l-carboxylate (0.69 g, 3.69 mmol) is added followed immediately by triethylamine (2.1 mL, 14.75 mmol). The reaction mixture is allowed to warm to room temperature, diluted with DCM (30 mL), washed with water, dried (Na

Molecular Weight:185.22
XLogP3:0.4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:185.10519334
Monoisotopic Mass:185.10519334
Topological Polar Surface Area:46.6
Heavy Atom Count:13
Complexity:213
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes