Preparation method of dexamethasone intermediate
A technology for dexamethasone and intermediates, which is applied in the field of preparation of dexamethasone intermediate methyltetraene, can solve the problems affecting the healthy development of saponin industry, outstanding environmental protection problems, long process routes, etc., and achieves novel design, Low environmental impact and high overall yield
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Embodiment 1
[0031] (Example 1: Preparation of Compound P1).
[0032]
[0033] Add 31.1g of 17β-cyano-17α-hydroxyandrost-4,9-dien-3-one (0.1mol) and 400mL of anhydrous methanol into a 1L three-necked flask, stir at 0°C for 10min, then Add 18.7mL of boron trifluoride diethyl ether solution (0.15mol) dropwise within 20min, then add 17mL of ethanedithiol (0.2mol) dropwise within 20min, stir and react at 0°C for 3h, and TLC detects that the reaction of the raw materials is complete , stop responding.
[0034] The reacted material was poured into 2L of water, a large amount of light yellow solid precipitated out, filtered with suction, the filter cake was rinsed with 2L of water first, then rinsed with 100mL of methanol at a temperature of 0°C, and finally vacuum-dried to obtain 37.0 g of compound P1, the mass yield was 119.0%, the molar yield was 95.6%, and the purity was 94.6% (HPLC).
[0035] 1 HNMR: (400MHz, CDCl 3 )δ5.50(s,2H),3.37(s,3H),3.23(dt,J=11.7,8.3Hz,1H),2.49-2.30(m,3H),2.26...
Embodiment 2
[0036] (Example 2: Preparation of Compound P2).
[0037]
[0038]Add 1.94g of compound P1 (5mmol), 1.7g of imidazole (25mmol), 1.5g of anhydrous magnesium sulfate and 25mL of DMF into a 100mL one-necked flask, stir and dissolve at room temperature (15-25°C, the same below) and then add 3mL Chlorotrimethylsilane (25 mmol) was heated to 50° C. for 12 h, and TLC detected that the reaction of the raw materials was complete, and the reaction was stopped.
[0039] The reacted material was cooled to room temperature, 150mL of water was added, and the layers were separated. The aqueous phase was extracted with ethyl acetate (30mL×3) and the organic phase was combined, washed successively with saturated sodium bicarbonate solution (40mL×2), saturated Wash with sodium chloride solution (30 mL), dry over anhydrous sodium sulfate, concentrate under reduced pressure, and dry in vacuo to obtain 2.29 g of off-white solid compound P2 with a mass yield of 118.0%, a molar yield of 99.1%, and...
Embodiment 3
[0041] (Example 3: Preparation of compound P3).
[0042]
[0043] Add 2g of compound P2 (4.34mmol) and 80mL of anhydrous isopropyl ether in a 250mL three-necked flask, stir and dissolve at room temperature under nitrogen protection, then add 30mL of methylmagnesium chloride (86mmol) with a concentration of 3M, the solution is cloudy now, and the temperature is raised After reflux reaction for 20 h, TLC detected that the reaction of raw materials was complete, and the reaction was stopped.
[0044] Cool the reacted material to 0°C, add 50mL of saturated ammonium chloride solution dropwise within 20min, stir for 30min, let stand to separate layers, extract the aqueous phase with ethyl acetate (30mL×4) and combine the organic phases, sequentially use saturated Washed with sodium chloride solution (15 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and dried in vacuo to obtain 2.11 g of crude compound P3 as a pale yellow solid with a mass yield of...
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