3-O-Ethylascorbic acid

The above 3-O-ethyl-5, 6-O-isopropylideneascorbic acid 40g dissolved in 200ml of ethanol. 10g of cation-exchange resin was added and was refluxed for 2 hours. The catalyst was removed by an ion exchange resin and concentrated under reduced pressure. After drying, with ethyl acetate: hexane (3: 1) crystallization. After drying, obtained 33.3g 3-O-ethylascorbic acid, yield 94percent. It was recrystallized in 100mL ethyl acetate giving 30.6g, yield 87percent, mp: 112-114°C.12.4 g of the 3-0-ethyl-isopropylidene ascorbic acid obtained in was dissolved in 100 ml of distilled water, to which 10 ml of 2N hydrochloric acid solution was added. The mixture was reacted at 60Formula I (10 g, 0.465 mol) was dissolved in 172 mL of dimethylformamide and then sodium bicarbonate (102 g, 1.605 mol) was added, followed by addition of ethyl tosylate (81 g, 0.404 mol), nitrogen was in purged. The reaction mixture was stirred at 60° C. for 10 hours. After cooled to the room temperature, sodium bicarbonate and salt were filtered and evaporated. After evaporation, 5percent sodium bicarbonate (100 mL) was added into crude and extracted for twice with Toluene. The organic phase was washed with water and evaporated. Crystallization from n-heptane gave 55 g formula II (0.225 mol; yield=65percent). Intermediate was dissolved in n-propanol (60 mL) and then added 2N HCl (16.9 mL), heat to 60° C., after 2 hours, the solvent was evaporated. re-crystallization from Toluene and n-propanol gave 35 g of formula (III). (0.172 mol; yield 56percent)The optimal reaction conditions were applied toscale-up the 3-O-ethylation of ascorbic acid. Sodiumascorbate (1.98 g, 10.0 mmol) was dissolved in DMSO(50 mL) and was stirred for 10 min at 50 °C. After addingethyl bromide (896 μL, 12.0 mmol), the mixturewas further stirred for 3.5 h at 50 °C. The reaction mixturewas diluted twofold with water and was subjectedto column chromatography to remove DMSO and unreactedstarting materials. The diluted reaction mixturewas chromatographed in a DIAION HP20 column( 3.0 × 33 cm; Mitsubishi Chemical Co., Tokyo) eluted with a stepwise gradient of MeOH-H2O solvent system(0, 10, 20, and 30percent, v/v). The 3-O-ethylascorbic acidcontainingfraction (30percent MeOH eluate) was concentratedto dryness. The residue was recrystallized fromEtOAc to obtain 1.04 g (51.0percent yield) of 3-O-ethylascorbicacid. The results of analysis of the purified compoundby 1HNMR, HRMS, and optical rotation areshown as follows. 1HNMR (600MHz, CD3OD) δΗ:1.41 (3H, t, J = 7.2 Hz), 3.69 (2H, d, J = 6.6 Hz), 3.88(1H, dt, J = 1.8, 6.6 Hz), 4.59 (2H, q, J = 7.2 Hz), 4.81(1H, d, J = 1.8 Hz). ESI-HRMS m/z [M−H]−: calcd forC8H11O6: 203.0561, found: 203.0562. [α]25D + 48.1°(c 1.0, MeOH). The product was determined to be3-O-ethylascorbic acid by its 1HNMR spectrum andmass spectrum, and by comparing the 1HNMR spectrumwith that in a previous report.10) The results indicatethat the described method here enables preparationof 3-O-ethylascorbic acid very easily and quickly comparedwith the conventional method, 10) and suggest thatthe simple single-step synthesis of 3-O-ethylascorbicacid can be applied to the procedure of a large scale.Preparation of L-?-?-lipoyl-3-ethyl-ascorbic acid8.15 g of L-3-ethyl-ascorbic acid (yield: 87 percent) was prepared in the same manner as in Step 1 of Example 5, except that 5.00 g of bromo ethane was used instead of polyethylene glycol bromide. Preparation of L-2-?-lipoyl-3-ethyl-ascorbic acid. Step 1. Preparation of L-3-polyethylene glycol-ascorbic acid 5.O g of bromo ethane and 0.97 g of ascorbic acid were added to 30 ml of dimethylformamide. 0.98 g of potassium carbonate was added to the reaction mixture, which was then stirred at room temperature overnight. The resultant was distilled under reduced pressure, and 100 ml of ethyl acetate was added to the resulting residue. The resultant was washed three times with 1 N hydrochloric acid and water. The resultant was distilled under reduced pressure to remove the solvent and dried in vacuo to obtain 4.06 g of L-3-ethyl-ascorbic acid (yield: 69percent).

Molecular Weight:204.18
XLogP3:-1.5
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:4
Exact Mass:204.06338810
Monoisotopic Mass:204.06338810
Topological Polar Surface Area:96.2
Heavy Atom Count:14
Complexity:259
Defined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes