Diethyl2,2-difluoromalonate

In the stainless steel pressure reactor (50 ml) in, adding magneton, 2 - amino isobutyric acid (1g, 9.7mmol), anhydrous pyridine (15 ml), two fluorine third acid diethyl ester (1.6 ml, 9 . 7mmol), argon replacement system 3 to turn off the reaction kettle, in oil bath heated to 200 C and maintain 2h, out of the reaction solution after cooling, in the rotary evaporator to remove the pyridine, obtaining oil objects, adding 3 mol/L hydrochloric acid (5 ml) adjusted to pH2 - 3, separating out a large quantity of solid, low warm settlement 1h after filtering, a small amount of b the nitrile washes cake three times, to obtain white solid powder after drying weighing 2.5g, yield 83%.Diethyl difluoropropanedioate (2.87 ml, 17.23 mmol) was dissolved in MeOH (20 mL) and a solution of 2, 3-dihvdro-1H-inden-2-ainine (2.07 g, 15.51 mmol) in MeOH (15mL) was added dropwise. The reaction was stirred at RT for 14 h. The reaction wasconcentrated and purified by Biotage FCC (50 g SNAP KP-Si02, 0-50% EtOAc in Heptanes)affording the title compound as a pale brown solid (1.79 g, 91% purity, 35%)?H NMR (500 MHz, DMSO-d6) 9.48 (d, J = 6.9 Hz, 1H), 7.22 (dcl, J = 5.3, 3.4 Hz, 2H), 7.15 (dd, J = 5.5, 3.2 Hz, 2H), 4.60-4.48 (in, IH). 3.88 (s, 3H), 3.20 (dd, .J= 15.9, 7.9Hz, 2H), 2.91 (dd, J= 15.9, 6.6 Hz, 2H). LCMS Method C: rt 1.09 mm, 91%, m/z 269.95(MW)5 g (1.0 eq., 25.49 mmol) of the compound 37 was dissolved in 40 mL of methanol, and 30 mL of methanol solution of sodium hydroxide (1.43 g (1.0 eq., 25.49 mmol)) was added dropwise thereto. It was then stirred for 3 hours at room temperature. After confirming by TLC the disappearance of the reacting materials, benzyl amine (8.4 mL (3.0 eq., 76.47 mmol)) was added and stirred overnight at 55 C. The reaction solution was concentrated under reduced pressure by using an evaporator, and the precipitated solids were added with diethyl ether followed by washing and filtering. The washed solids were dissolved in 1 M HCl. Then, liquid fractionation extraction was performed 3 times using ethyl acetate. The collected organic layer was washed with a saturated aqueous solution of NaCl. After drying over magnesium sulfate, it was concentrated under reduced pressure by using an evaporator in water bath at 40 C. to obtain the residues (compound 39). It was directly subjected to the following reducing reaction.

Molecular Weight:196.15
XLogP3:1.2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:6
Exact Mass:196.05471512
Monoisotopic Mass:196.05471512
Topological Polar Surface Area:52.6
Heavy Atom Count:13
Complexity:183
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes