1,1-Dimethylethyl 3-[(dimethylamino)methylene]-4-oxo-1-pyrrolidinecarboxylate

Step 1: Synthesis of tert-butyl 3-((dimethylamino)methylene)-4- oxopyrrolidine– 1-carboxylate. A suspension of tert-butyl 3-oxopyrrolidine-1-carboxylate (10 g, 54.05 mmol) in 1, 1-dimethoxy-N, N-dimethylmethanamine (120 mL) was stirred at 105°C for 1 h., cooled down to room temperature, the solvent was removed in vacuo and the residue was purified by chromatographic column on silicagel (DCM/MeOH = 60/1 to 20/1) to give tert-butyl 3-((di-methyl- amino)methylene)-4-oxopyrrolidine-1-carboxylate (10.78 g, 83percent yield). ESI-LCMS (m/z): 241.2[M+1]Preparation 31 Preparation 31 The 3-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (40g, 216mmol) was dissolved in 300ml DMF-DMA was heated at 105 deg. C 40 minutes. The solution was cooled and evaporated under reduced pressure, hexane was added, and filtered to give an orange solid 41g, and dried, it was used for the next reaction without purification.(0086) 3-oxopyrrolidine-1-tert-butyl carboxylate (40g, 216mmol) was dissolved in 300mL DMF-DMA, heated for 40 minutes at 105°C. Cooled and concentrated to dry under vacuum, treated with hexane, filtered to obtain orange solid 41g, dried, the product can be used in the reaction of the next step without purification.A solution of N-Boc-3-pyrrolidinone (CAS Number 101385-93-7; 5.0 g, 27.0 mmol) in DMF- DMA (32.17 g, 270 mmol) was heated at 100°C for 1.5 h. The resulting mixture was cooled to rt and concentrated under reduced pressure. The obtained residue was triturated with n-pentane (100 ml). The resulting solid was dried under high vacuum yielding tert-butyl 3-((dimethylamino)methylene)-4- oxopyrrolidine-l-carboxylate (4.700 g, 19.58 mmol). LCMS: Method 1, 1.556 min, MS: ES+ 241.43.Step (1) 70kg of tetrahydrofuran was added to the 200L reaction vessel, was added 1-tert-butoxycarbonyl-3-pyrrolidinone 6.9kg, then added with DMF-DMA 13.5kg, stirred and heated to reflux for 3 hours, TLC sheet monitoring point, after the reaction, was cooled to room temperature. Concentrated under reduced pressure, and dried to give a reddish brown solid 7.3kg, a yield of 81.5percent; was used directly in the next step.The 3 - oxo-pyrrolidine -1 - carboxylic acid tert-butyl (40g, 216mmol) dissolved in 300 ml DMF - DMA, in 105 °C lower heating 40 minutes. Cooling and depressurization evaporation of the solution, the use of hexane processing, filter and get the orange solid 41g, drying, do not need purification can be used for the next step reaction.

Molecular Weight:240.30
XLogP3:0.9
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:240.14739250
Monoisotopic Mass:240.14739250
Topological Polar Surface Area:49.8
Heavy Atom Count:17
Complexity:353
Defined Bond Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes