Category: 444-14-4

Reference of 444-14-4,Some common heterocyclic compound, 444-14-4, name is 2-Bromo-4,6-difluoroaniline, molecular formula is C6H4BrF2N, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Dissolve 2-bromo-4,6-difluoroaniline (40 g, 192 mmol) in methyldisulfide (250 mL) and heat to 75 C under nitrogen. Add isoamyl nitrite (67 mL, 500 mmol) dropwise via an addition funnel trough a reflux condenser (-1 drop/sec). Large exotherm may occur if addition is too fast. After addition is complete, heat the reaction to 95 C for 1 hour and cool to room temperature and concentrate in vacuo. Purify dark brown residue via silica gel chromatography eluting with hexanes to yield 30.3 g of 1-bromo-3, 5- difluoro-2-methylsulfanyl-benzene (66%). Charge a flask with isopropyl magnesium chloride (145 mL, 2M in THF, 290 mmol) and dilute with tetrahydrofuran (150 mL) and heat to 40 C under nitrogen. Add 1-bromo-3, 5-difluoro-2-methylsulfanyl-benzene (28 g, 117 mmol) slowly over 5 minutes. After 30 minutes, cool the reaction to 0 C and add trimethylborate (46 mL, 410 mmol) diluted with tetrahydrofuran (100 mL) via an addition funnel over 5 minutes. Partition the resulting gelatinous mixture between methylene chloride and 1N HC1. Acidify the aqueous layer to pH-1 (if needed) and vigorously stir the biphasic mixture until all solids are dissolved. the organic layer. Dry over sodium sulfate, filter and concentrate. Triturate with hexanes and filter to yield 14.7 g (61 %) of the title compound.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-4,6-difluoroaniline, its application will become more common.

Reference:
Patent; ELI LILLY AND COMPANY; WO2005/73204; (2005); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Electric Literature of 444-14-4,Some common heterocyclic compound, 444-14-4, name is 2-Bromo-4,6-difluoroaniline, molecular formula is C6H4BrF2N, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Dissolve 2-bromo-4,6-difluoroaniline (40 g, 192 mmol) in methyldisulfide (250 mL) and heat to 75 C under nitrogen. Add isoamyl nitrite (67 mL, 500 mmol) dropwise via an addition funnel trough a reflux condenser (-1 drop/sec). Large exotherm may occur if addition is too fast. After addition is complete, heat the reaction to 95 C for 1 hour and cool to room temperature and concentrate in vacuo. Purify dark brown residue via silica gel chromatography eluting with hexanes to yield 30.3 g of 1-bromo-3, 5- difluoro-2-methylsulfanyl-benzene (66%). Charge a flask with isopropyl magnesium chloride (145 mL, 2M in THF, 290 mmol) and dilute with tetrahydrofuran (150 mL) and heat to 40 C under nitrogen. Add 1-bromo-3, 5-difluoro-2-methylsulfanyl-benzene (28 g, 117 mmol) slowly over 5 minutes. After 30 minutes, cool the reaction to 0 C and add trimethylborate (46 mL, 410 mmol) diluted with tetrahydrofuran (100 mL) via an addition funnel over 5 minutes. Partition the resulting gelatinous mixture between methylene chloride and 1N HC1. Acidify the aqueous layer to pH-1 (if needed) and vigorously stir the biphasic mixture until all solids are dissolved. the organic layer. Dry over sodium sulfate, filter and concentrate. Triturate with hexanes and filter to yield 14.7 g (61 %) of the title compound.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-4,6-difluoroaniline, its application will become more common.

Reference:
Patent; ELI LILLY AND COMPANY; WO2005/73204; (2005); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 444-14-4, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 444-14-4 as follows.

The procedure was adapted from Lemair, M. et.al . Tetrahedron, 2011 67, 1971 1976. To the solution of 2-(trifluoromethyl)aniline (1.5 g, 9.31 mmol) inacetic acid (15 mL) was added KBr (1.307 g, 10.99 mmol) and sodium perborate monohydrate (0.929 g, 9.31 mmol) and the mixture was stirred for 5 mm. To this mixture was added ammonium molybdate tetrahydrate (11.51 g, 9.31 mmol) and the reaction mixture was stirred at room temperature for 3 h. After completion of the reaction as determined by TLC, water was added and the pH was adjusted to 8 usingaq. saturated sodium bicarbonate solution. The reaction mixture was extracted with ethyl acetate (3 x 5 mL). The combined organic extracts were washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to afford 4-bromo-2-(trifluoromethyl)aniline (800 mg, 36% yield) as a yellow solid. The analytical data was consistent with the literature reference cited above.

According to the analysis of related databases, 444-14-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; HARTZ, Richard A.; AHUJA, Vijay T.; BRONSON, Joanne J.; DZIERBA, Carolyn Diane; MACOR, John E.; NARA, Susheel Jethanand; RAJAMANI, Ramkumar; WO2015/6100; (2015); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Adding a certain compound to certain chemical reactions, such as: 444-14-4, name is 2-Bromo-4,6-difluoroaniline, belongs to bromides-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 444-14-4, HPLC of Formula: C6H4BrF2N

Commercially available bromodifluoroaniline (11) is treated with di-tert-butyldicarbonate to give protected aniline 12. Alkylation of aniline 12 gives the N-ethyl derivative 13, which is converted to the lithium derivative by metal halogen exchange, and added to the Boc-protected aziridine 3a under copper catalysis, yielding intermediate 14. The acetal protecting group is removed and the resulting diol 15 is converted to epoxide 16 using well-known procedures.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; ELAN PHARMACEUTICALS, INC.; WO2005/87752; (2005); A2;,
Bromide – Wikipedia,
bromide – Wiktionary

A common heterocyclic compound, 444-14-4, name is 2-Bromo-4,6-difluoroaniline, molecular formula is C6H4BrF2N, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. 444-14-4.

3. Amination The 1-bromo-3,5-difluorobenzene generated by diazotization of 2-bromo-4,6-difluoroaniline can be converted to 100 lbs. of 3,5-difluoroaniline as follows: A suitable pressure reactor designed for a minimum of 300 psig pressure is charged with 288.1 lbs. of 29% aqueous ammonia. The reactor is designed to provide for pressure control via temperature control of the reaction. To the ammonia charge, 4.7 lbs. of cuprous oxide is added, and the 168.2 lbs. of crude 1-bromo-3,5-difluorobenzene product is added. The reaction mixture is heated to about 135 C. using temperature control to maintain a maximum pressure of 300 psig, and the reaction pressure is maintained at about 300 psig by slowly increasing the reaction temperature to 165 C. over 4.5 hours. The reaction mixture is held at 165 C. for one additional hour, and then a sample is assayed for completeness of the reaction. If more than 0.5% by weight of 1-bromo-3,5-difluorobenzene remains unreacted, then the reaction mixture is held at 165 C. for one more hour and re-assayed. This process is repeated until less than 0.5% by weight of unreacted 1-bromo-3,5-difluorobenzene remains.

The synthetic route of 2-Bromo-4,6-difluoroaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BASF Corporation; US5977412; (1999); A;,
Bromide – Wikipedia,
bromide – Wiktionary