With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.1355338-16-7, name is 2-(4-Amino-3-fluorophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol, molecular formula is C9H6F7NO, molecular weight is 277.14, as common compound, the synthetic route is as follows.HPLC of Formula: C9H6F7NO
Intermediate 14: tert-Butyl 1-{[2-fluoro-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]carbamoyl}-5-(methylsulfonyl)-1,3-dihydro-2H-isoindole-2-carboxylate (0646) (0647) 2-(tert-Butoxycarbonyl)-5-(methylsulfonyl)isoindoline-1-carboxylic acid (345 mg, 1.01 mmol) was suspended in DCM (5 mL) and to this 2-(4-amino-3-fluorophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (280 mg, 1.01 mmol) and triethylamine (0.282 mL, 2.02 mmol) was added. To the resulting solution T3P (1.203 mL, 2.02 mmol) 50% in EtOAc was then added. The reaction was stirred at rt for 30 mins. LCMS indicated complete conversion to product. The reaction was diluted with DCM and washed with 0.5M HCl. The layers were separated using a phase separator and concentrated in vacuo. The residue was purified on silica eluting with 40% EtOAc in heptane. Completely pure fractions were combined and concentrated in vacuo to afford tert-butyl 1-((2-fluoro-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)carbamoyl)-5-(methylsulfonyl)isoindoline-2-carboxylate (402 mg, 66.3%) as a solid. (0648) LC/MS: m/z=601 [M+H]+. 1H NMR (500 MHz, DMSO-d6, mixture of rotamers, 2*:1) delta 1.38*, 1.47 (s, 9H), 3.21, 3.23*(s, 3H), 4.7-4.85 (m, 2H), 5.81*, 5.85 (s, 1H), 7.42-7.58 (m, 2H), 7.67*, 7.72 (d, 1H), 7.88-8.06 (m, 3H), 8.92 (s, 1H), 10.60, 10.63*(s, 1H).
At the same time, in my other blogs, there are other synthetic methods of this type of compound,1355338-16-7, 2-(4-Amino-3-fluorophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol, and friends who are interested can also refer to it.
Reference:
Patent; AstraZeneca AB; NARJES, Frank; OLSSON, Roine Ingemar; VON BERG, Stefan; LEVER, Sarah; (112 pag.)US2017/166527; (2017); A1;,
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