Tert-Butyl (4R-cis)-6-formaldehydel-2,2-dimethyl-1,3-dioxane-4-acetate

(4R-cis)-6-(hydroxymethyl)-2, 2-dimethyl- 1 , 3 -dioxane-4-acetic acid, 1 , 1 -dimethyl ethyl ester (10.0 g , 0.0385 mol) mol) was dissolved in dimethyl sulfoxide (15.0 g , 0.192 mol) and dichloromethane (100 ml) followed by cooling at 0 to -5 (6-Formyl-2, 2-dimethyl- [1, 3] dioxan-4-yl)-acetic acid tert-butyl ester To a solution of (6-hydroxymethyl-2. 2-dimethyl-11, 3] dioxan-4-yl)-acetic acid tert- butyl ester (30.0 g, 115 mmol) at 0 °C in DCM: MeCN (10: 1, 225 mL) was added 4 A molecular sieves (55 g), 4-methylmorpholine N-oxide (20. 3 g, 172.9 mmol) and tetrapropylammonium perruthenate (0.41 g, 1. 15 mmol). The reaction was warmed from 0 °C to 25 °C over 0.5 hr and then stirred at that temperature for 5 hrs. Once complete, as determined by TLC, the reaction mixture was filtered through celite and the filtrate was concentrated to a brown oil that was purified by silica gel chromatography (20-70 percent EtOAc/Hexane) to provide (6-formyl-2, 2-dimethyl- [1, 3] dioxan-4-yl)-acetic acid tert-butyl ester (25.5 g, 86percent): H-NMR (CDCI3) 09. 54 (s, 1 H), 4.30-4. 26 (m, 2 H), 2.45-2. 39 (m, 1 H), 2.33-2. 27 (m, 1 H), 1.81-1. 77 (m, 1 H), 1.46-1. 41 (m, 16 H), 1.28-1. 20 (m, 1 H).(2) step (1) to obtain compound II of the methylene chloride solution, adding 0.15g (0.99mmol) TEMPO, 2.36g (0.0198mol) potassium bromide and 16.6g (0.198mol) sodium bicarbonate, stirring and mixing after cooling to -15 °C, dropping pre-adjusting the pH to 10 sodium hypochlorite solution (175.9g (0.238mol) sodium hypochlorite solution (content 10.9percent) in terms of mass percentage concentration is 5percent sulfuric acid adjusted to pH 10), control reaction solution temperaturethe <0 °C.drop finishes, 0 °C stirring for reaction, GC tracking of the reaction, the response finishes (compound III less than0.2percent)adding quality percentage concentration is 10percent aqueous solution of sodium thiosulfate 156.5g stirring quenching reaction, the resulting organic phase after transferring, to 300g × 2 washing, to obtain light yellow clear solution, adding 50g drying by anhydrous sodium sulfate, filter, to 20g dichloromethane wash the filter cake, the spin vaporization (40 °C, -0.09 MPa) unless the solvent to obtain strawcoloured solid 46.0g, yield 90.1percent, GC purity 98.7percent, crude I is compound;0.02 g of TEMPO (2, 2, 6, 6-tetramethyl-1-piperidinyloxy free radical), 0.96 g of potassium bromide, 18.6 g of sodium hydrogencarbonate and 50 ml of methylene chloride were placed in a 500 ml flask, Stirred at ~ 5 ° C.After dissolving 11.64 g (44.71 mmol) of t-butyl 2 - [(4R, 6S) -6-hydroxymethyl-2, 2-dimethyl- 1, 3-dioxane- 4-yl] acetate in 50 ml of methylene chloride , Added to the above reaction. After cooling the reaction product to -15 ° C. or lower, 36.6 ml (53.65 mmol, 1.2 equivalent) of a 10.9percent (w / w) sodium hypochlorite aqueous solution was added dropwise at once. After the dropwise addition, stirring was carried out at 0 ° C. for 1 hour, the reaction progress degree was checked by gas chromatography (GC), the reaction product was filtered under reduced pressure, 10percent sodium thiosulfate solution (10 w / wpercent sodium thiosulfate solution) 100 ml was added and the organic layer was separated. 100 ml of a saturated sodium chloride solution was added to the organic layer, and the organic layer was further separated. After adding 150 ml of water to the organic layer and stirring for 10 minutes, the stagnant organic layer was separated, dried over anhydrous magnesium sulfate, filtered, methylene chloride as an organic solvent was distilled under reduced pressure at 40 ° C. and 3 cmHg for 10 minutes To obtain a concentrated residue 1 as an oil phase (step A).The concentrated residue 1 was adjusted to a pressure of 3 cmHg in a vacuum vacuum dryer and dried for 30 minutes at 80 ° C. without separately adjusting the humidity to obtain the title compound as pale brown crystals (Step B) . (The XRD graph of the product is shown in Figure 1 and its value is as shown in Figure 2. The DSC value of the product is shown in Figure 3.) Yield of product 83percent (8.2kg)Reference tert-Butyl 2-[(4R, 6S)-6-formyl-2, 2-dimeihyl-1, 3-dioxane-4-yl] acetate To a dispersion of tert-butyl 2-[(4R, 6S)-6-hydroxymethyl-2, 2-dimethyl-1, 3-dioxane-4-yl] acetate (15 g, 57.6 mmol), sodium hydrogencarbonate (13.6 g, 161.3 mmol), potassium bromide (1.37 g, 11.5 mmol) and 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-1-oxyl free radical (248 mg, 1.44 mol) in ethyl acetate (150 ml), an aqueous solution of sodium hypochlorite (44.2 g, 16.7wtpercent, 70.2 mmol) was added under nitrogen stream at -10°C carefully dropwise to keep the inner temperature within 5°C. After the dropwise addition, the mixture was stirred at 0°C for 1 hour and the aqueous layer was separated. The organic layer was further diluted with ethyl acetate (100 ml), and sequentially washed with a 5percent sodium thiosulfate aqueous solution (75 ml) and water (40 ml .x. 2). Then, the organic layer was dried with anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure, and the obtained crude product was purified with silica gel column chromatography (silica gel: 200 g, developing solvent: hexane / ethyl acetate = 2 / 1 by volume) to obtain the title compound (8.0 g, yield: 54percent) as white crystals. Preparation of Tert-Butyl 3, 5-Dideoxy-2, 4-O-(1-Methylethylidene)-L-Erythro-Hexuronate

Molecular Weight:258.31
XLogP3:1.2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:5
Exact Mass:258.14672380
Monoisotopic Mass:258.14672380
Topological Polar Surface Area:61.8
Heavy Atom Count:18
Complexity:316
Defined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes