TRIMETHYLSULFOXONIUM BROMIDE

(2), At 0 C, To a solution of (1), At 0 C, To a solution of trimethylsulfonium bromide (0.41 mol, 70.9 g) in DMSO (800 mL), Add NaOH (0.41 mol, 16.4 g), The reaction solution was stirred at room temperature for 30 minutes.Reduce the temperature to 0 C, A solution of Compound I (0.4 mol, 100 g) in DMSO (200 mL) was added to the mixture.The reaction was stirred at 40 C for 12 hours.Water was added to the reaction mixture, followed by extraction with ethyl acetate.The organic phase was concentrated to give compound V (98.3 g).The nuclear magnetic data is as follows.Colorless oil, 91% content, The yield was 85%.Add 450 parts of DMF to the reaction kettle.Adding 120 parts of the ketal, 80 parts of trimethyl sulfoxide, Stir well, Add 27 parts of caustic soda at 42-45 C, Add the reaction for 3 hours, Add a dilute sulfuric acid with a mass fraction of 20% to adjust the pH to 2, Hydrolyzed for 2 hours, after the hydrolysis, the material was pumped to the water-discharging kettle for water precipitation and centrifugation.Washing to neutral, putting into the drying device, starting the infrared heating tube 6, After 8 minutes of illumination, the motor 19 is controlled to rotate at 800-1000 r/min.Continuous operation for 10 minutes to obtain a cyclopropyl hydrolyzate;A 200 mL four-necked flask was equipped with a stirrer, And a platinum thermometer were set, 40 mL of dry tetrahydrofuran (hereinafter also referred to as THF)3.81 g (39.7 mM, 2.1 eq) of sodium tert-butoxide (hereinafter also referred to as t-BuONa) was added.Subsequently, 6.87 g (39.7 mM, 2.1 eq) of 1000mL reaction flask was added compound I 85.9g (1.0mol), Trimethylsulfoxonium bromide 70.0 g (1.05 mol), 1, 2, 4-triazole 31.9 g (1.20 mol), Potassium hydroxide solution KOH (2.82 mol) (60.9 g KOH in 345 mL water) was added with stirring.With 345 mL of isopropanol, heat up to 60C and hold at 60-65C for 3 hours.Less than 1% of the starting material was detected by HPLC, heating was stopped, and isopropanol was removed by vortexing at 50C.To the remaining product after adding 345mL of water cooling down to 15 C below, A 10% HCl solution was added dropwise to adjust the pH of the system to neutrality, and a solid precipitated in the aqueous phase.Dissolved and extracted with ethyl acetate 688mLThe solid was not completely dissolved, liquid separation, the aqueous phase was extracted with ethyl acetate 172mL × 6, the combined ethyl acetate phase, The ethyl acetate phase was extracted with 5% HCl solution 260 mL x 2 and the HCl solution was combined.Wash with ethyl acetate 172 mL×2, wash with toluene 172 mL, and stir with 4.3 g of activated carbon.Pad diatomaceous earth filtration, washing, cooling filtrate cooling below 10 , Add ammonia to adjust pH to neutral, Stir the crystals with heat and stir, filter, and solids are stirred and pumped with 170 mL of water to obtain a white solid.Vacuum heated (80C) to obtain crude fluconazole, 82.5g white solid, Purity 89.8%, yield 80%.Compound (II-1) (48.6mmol) N, N- dimethylacetamide ( 30 mL) And it was dissolved in water (2.3mL), and the temperature was raised to 65C . Here , compound (III-1) (63.3mmol), (2) Production Example 2-2 (0100) 3.24 mmol of compound 4-a was dissolved in 3.2 mL of dimethylacetamide, and heated to 85 C. 4.85 mmol of a sodium salt of 1, 2, 4-triazole and 4.53 mmol of (1) Production Example 2-1 (0098) 3.26 mmol of compound 4-a was dissolved in 3.2 mL of dimethylacetamide, and heated to 85 C. 4.91 mmol of a sodium salt of 1, 2, 4-triazole was added to the obtained solution. Next, 1.99 mmol of a 28% methanol solution of sodium methoxide and 4.78 mmol of Production Synthesis of 2-(4-chlorobenzyl)-8, 8-dimethyl-1-(1H-1, 2, 4-triazol-1-ylmethyl)-7, 9-dioxaspiro[4, 5]decan-1-ol (compound V-1; azole derivative (Vb) in which R3=CH3, R4=CH3, p=1, q=1, Xm=4-Cl, A=N) In dehydrated N, N-dimethylacetamide (6.18 mL), 1, 2, 4-triazole (compound I-1; compound (I) in which A=N) (15.0 mmol) was dissolved and the mixture was heated to 85 C. Thereafter, a 28% sodium methoxide methanol solution (15.0 mmol) was added thereto, and the mixture was heated and stirred at 85 C. for 3 hours. To the obtained reaction solution, 2-(4-chlorobenzyl)-8, 8-dimethyl-7, 9-dioxaspiro[4, 5]decan-1-one (compound III-1; compound (IIIb) in which R3=CH3, R4=CH3, p=1, q=1, Xm=4-Cl) (10.0 mmol) and [0089] First, after NaH (0.91 g (ca. 60% in mineral oil)) was suspended in N-methylpyrrolidone (NMP) (8 mL), 1, 2, 4-triazole (1.67 g) was added and stirred for 0.5 hours to produce a sodium salt. Next, compound (4) (5.00 g) was added.After this was heated to approximately 90C (bath temperature), [1, 2, 4]-triazolesodium salt (1.14g) was dissolved in N-methylpyrrolidinone (6.4 ml), and heated to an internal temperature of 115C. 2-(4-chlorobenzyl)-8, 8-dimethyl-7, 9-dioxaspiro[4, 5]decane-1-o n (azole derivative (VIII'), R6=CH3, R7=CH3, Xm=4-Cl, A=N) (2.59 g) was added to this, and the mixture was washed thoroughly with N-methylpyrrolidinone (2.0 ml). After the internal temperature was back to 115C, sodium t-butoxide (725 mg) and

Molecular Weight:173.07
Hydrogen Bond Acceptor Count:2
Exact Mass:171.95575
Monoisotopic Mass:171.95575
Topological Polar Surface Area:18.1
Heavy Atom Count:6
Complexity:53
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes