Extended knowledge of 627526-90-3

Reference of 627526-90-3, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 627526-90-3, name is 1-Bromo-3-(difluoromethyl)-5-fluorobenzene, This compound has unique chemical properties. The synthetic route is as follows.

steps 3-5; – /?-Methoxybenzyl alcohol (36.8 g, 266.7 mmol) was added slowly to a mixture of potassium t-butoxide (28.7 g, 255.5 mol) and THF (250 mL). After stirring for about 15 min, 30 (50.O g, 222.2 mmol) was added and the reaction mixture heated to about 65 C. After stirring at 65 C for 2 h, the reaction is analyzed by HPLC. After cooling to RT, a mixture of saturated NaHCO3 solution (150 mL) and water (150 mL) was added. Toluene (300 mL) was added, the organic phase separated and washed with a mixture of saturated NaHCO3 solution (75 mL) and water (75 mL). Polish filtration and concentration in vacuo provided 83.9 g of crude 32 as an oil which is used without further purification.To a solution of crude 32 in NMP (180 ml) was added potassium ferrocyanide(31.1 g, 84.44 mmol) and Na2CO3 (23.55 g, 222.2 mmol). The resulting slurry was degassed thoroughly via repeated evacuation and purging with nitrogen. The slurry was heated to about 100 C and a solution of Pd(OAc)2 (150 mg, 0.67 mmol) and DPPF (505 mg, 0.91 mmol) in degassed NMP (20 mL) added. The mixture was heated to ca. 130 C for about 3 h. HPLC analysis indicated ca. 5% starting material remained. Additional Pd(OAc)2 (50 mg, 0.22 mmol) is added and heating at 130 C was continued for 1.5 h when HPLC analysis showed complete conversion.After cooling toluene (400 mL) and saturated sodium sulfite solution (10 mL) are added and mixture heated at ca. 40 C for about 1 h. Solka-floc (10 g) was added and the mixture was filtered through a bed of Solka-floc and the cake was washed with toluene {ca. 100 mL total). The filtrate was washed successively with dilute sodium sulfite solution (1 x 400 mL) and water (2 x 200 mL). The combined aqueous phases are extracted with toluene (1 x 100 mL) and the toluene back extracted with water (2 x 50 mL). The combined organic phases are polish filtered, and concentrated in vacuo to obtain 70.4 g of 34 as a dark-colored oil (70.4 g) which was used in the next step without further purification.To the solution of crude 36 in toluene (190 mL) and anisole (65 mL) is added TFA (25.3 g, 222.2 mmol). The reaction was heated to ca. 65 C and stirred for about 2 h until the reaction was complete by HPLC. The mixture was distilled in vacuo to remove most of the TFA. After cooling, the mixture is extracted twice with ca. 10% Na2CO3 solution (300 mL then 150 mL). The combined aqueous phases were acidified to a pH of 5.5 with con HCl and extracted with EtOAc (2 x 200 mL). The combined organic phases were washed with water (1 x 150 ml), polish filtered and the solvent replaced with toluene by vacuum distillation. The solution was concentrated to ca. 200 mL, then heptane (200 mL) was slowly added and the mixture heated to 80 C. The mixture was cooled to RT, aged overnight, filtered, and washed with 50% heptane in toluene {ca. 30 mL). The isolated product was dried in vacuo at ca. 60 C to afford 29.0 g (77.2% yield over 3 steps)of 36.

The chemical industry reduces the impact on the environment during synthesis 1-Bromo-3-(difluoromethyl)-5-fluorobenzene. I believe this compound will play a more active role in future production and life.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2008/145563; (2008); A2;,
Bromide – Wikipedia,
bromide – Wiktionary