581065-95-4, These common heterocyclic compound, 581065-95-4, name is tert-Butyl 1-amino-3,6,9,12-tetraoxapentadecan-15-oate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
In the glove box under an atmosphere of dry nitrogen, a 3000 mL, 4-necked flask was charged with bis-CBZ-Lysine (200.0 g, 483 mmol), EDC (139 g, 724 mmol), and 1500 mL of 2:1 tetrahydrofuran:tert-butyl methyl ether. The flask was fitted with an immersion well; the remaining joints were stoppered, and the flask was transferred to the fume hood where one of the stoppers was replaced with an addition funnel connected by a gas inlet adapter to a bleed of dry nitrogen. The flask was placed in a salted ice-water bath, fitted with an overhead stirring apparatus, and stirred until 0[deg.] C. was attained. In the glove box under a dry nitrogen atmosphere, amino-dPEG(R)4-TBE (163 g, 507 mmol) was dissolved in tetrahydrofuran (170 ml). The PN10221 was then poured into the addition funnel under a nitrogen shower and added slowly by drop, keeping the temperature as close to [deg.] C. as possible. The reaction was allowed to continue overnight, warming slowly to ambient. The reaction appeared complete the next morning by TLC and RP-HPLC. Stirring of the reaction mixture was stopped, and the EDU was allowed to settle for several hours. The solution was then decanted from the EDU goo. The reaction solvent was removed by rotary evaporation under reduced pressure at 45[deg.] C. The residue was then dissolved in dichloromethane to a final volume of 1400 mL and washed once with 250 mL with 10% aqueous HCl, then once with 400 mL of 5% brine. The DCM was removed by rotary evaporation at 35[deg.] C., and the residue was dried by rotary evaporation at 45[deg.] C. under high vacuum for about 1 hour. Yield: 330 gms (95.4%) HPLC (AMINES3045FF METHOD): 96.2% purity by ELSD. TLC: Ethyl Acetate:Methanol 8:2. Major spot at Rf=0.69 with both UV quench at 254 nm and iodine-positive reaction. One minor UV quenching spot (no iodine reaction) near solvent front. No ninhydrin-positive spot. NMR: (400 MHz, CDCl3, [delta]): 7.322 (m, 11H, 2 CBZ rings & NH); 6.737 (s, 1H, amide); 5.762 (s, 1H, amide); 5.084 (m, 4H, 2*CH2O from CBZ); 4.153 (q, 1H, CHN on lysine); 3.526 (t, 2H, CH2 to N on lysine sidechain); 3.425 (t, 2H, CH2 [beta] to N on dPEG(R)); 3.164 (t, 2H, CH2N on PEG); 2.478 (t, 2H, CH2CO on PEG); 1.467 (m, 15H, lysine side chain alkyl methylene groups plus t-butyl ester). Quantitative NMR purity=96.8%
Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 581065-95-4.
Reference:
Patent; UNIVERSITY OF WASHINGTON; QUANTA BIODESIGN, LTD.; Davis, Paul D.; Wilbur, D. Scott; US2013/52130; (2013); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics