The synthetic method of moxifloxacin chiral side chain intermediate
A technology of chiral side chains and synthesis methods, which is applied in the field of synthesis of moxifloxacin chiral side chain intermediates, can solve the problems of increasing side chain synthesis costs and high prices, and achieve novel route design, fast reaction speed, and side effects. The effect of less product
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Embodiment 1
[0020] The preparation route of compound I:
[0021]
[0022] The specific process is:
[0023] Add 1g (7.58mmol) of L-asparagine and 200mg Ru-C to a 50mL two-necked bottle, add 20mL of dilute hydrochloric acid (1mol / L), under low temperature H 2 After three replacements, the reaction was moved to room temperature and stirred, and the reaction was completed after 10 h. Add 1mol / L NaOH to adjust the pH of the solution to 8-9, extract the aqueous layer with ethyl acetate (60mL X 4), combine the organic layers, anhydrous NaSO 4 It was dried, filtered, concentrated and washed with ethyl acetate to obtain 0.74 g of off-white solid I with a yield of 82.77%. MS(m / z)119(M+1); 1 HNMR (400MHz, CD 3 OD)δ: 3.33(m,2H), 2.98(m,1H), 2.40(m,1H), 2.21(m,1H); 13 C NMR (100MHz, CD 3 OD) δ: 172.9, 62.5, 48.7, 36.2.
Embodiment 2
[0025] The preparation route of compound II:
[0026]
[0027] The specific process is:
[0028] Add 5g (42.37mmol) of compound I to a 250mL wedge-shaped flask, add 96mL of 1mol / L sodium hydroxide solution, and stir at 0°C. After 10min, add 5.94g (49.27mmol) of trimethylacetyl chloride Put it into the constant pressure dropping funnel, dissolve it with 35mL of 1,4-dioxane and add it to the system dropwise. After dropping, the reaction was moved to room temperature and stirred for 24 h, then the reaction was terminated. Extract the reaction solution with diethyl ether (60mL X 3), then move the reaction to 0°C, adjust the pH value of the solution to 1-2 with 3mol / L hydrochloric acid, a white granular solid precipitates, filter, and collect the filter cake; Ethyl acetate (60mL X 4) was extracted, the organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the solid obtained after evaporating off the solvent was mixed with the filter cake and evaporat...
Embodiment 3
[0030] The preparation route of compound III:
[0031]
[0032] The specific process is:
[0033]Add 0.5g (2.48mmol) of compound II and 129mg (3.22mmol) of sodium hydride into a 50mL two-necked flask, replace with nitrogen, add 35mL of dry tetrahydrofuran, and stir at 0°C. After 5min, add 0.48g (4.18mmol) of methanesulfonyl chloride, stir at room temperature for 20h, then add 129mg (3.22mmol) of sodium hydride to the system, and move the reaction to 50°C and stir for 26h, TLC monitoring (EA ) The basic reaction of raw materials is complete. After the solvent was rotary evaporated, 0.29 g of white solid was obtained by silica gel column chromatography (DCM / EA=1 / 1-EA), the yield was 63.7%. MS(m / z)185(M+1); 1 HNMR (400MHz, CDCl 3 )δ:5.42(s,2H),4.46-4.40(m,2H),4.19(m,1H),2.77(dd,J=16,8Hz,1H),2.57(dd,J=16,4Hz,1H ),1.21(s,9H); 13 C NMR (100MHz, CDCl 3 )δ: 178.8, 173.0, 47.4, 45.6, 44.8, 39.7, 28.4.
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