Reference of 874285-03-7,Some common heterocyclic compound, 874285-03-7, name is 3-Bromo-2-fluorophenylacetonitrile, molecular formula is C8H5BrFN, 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.
2-(3-bromo-2-fluorophenyl)acetonitrile (800 mg, 3.7 mmol,1 eq.) and (S)-1- iodo-2-(2-iodoethoxy)propane (1.27 g, 3.74 mmol, 1 eq.) were dissolved in dimethyl sulfoxide (10 ml_). Sodium hydride (331 mg, 8.3 mmol, 2.2 eq.) was added to the reaction mixture and stirred for 1 h at room temperature. The reaction mixture was diluted with water (10 ml_) and ethyl acetate (10 ml_), and the layers were separated. The organic phase was washed with 1 M HCI (1×10 ml_), water (1×10 ml_) and brine (1×10 ml_). The organic phase was concentrated under vacuum to afford a diastereomehc mixture of (2S,4R)-4- (3-bromo-2-fluorophenyl)-2-methyl-tetrahydro-2H-pyran-4-carbonitrile and (2S,4S)-4-(3-bromo-2-fluorophenyl)-2-methyl-tetrahydro-2/-/-pyran-4- carbonitrile (1 :1 ). The diastereomehc mixture was separated by reverse phase chromatography (40 – 90% acetonithle-water) to obtain the title compound (252 mg, 23%) as a single isomer. Stereochemistry confirmed by NMR. [2SAR)- 1 H NMR (400 MHz, CHLOROFORM-c/) delta ppm 1.26 (d, J=6.2 Hz, 3 H) 1.81 (dd, J=13.2, 11.0 Hz, 1 H) 2.08 – 2.26 (m, 3 H) 3.89 – 4.02 (m, 2H) 4.04 – 4.16 (m, 1 H) 6.99 – 7.13 (m, 1 H) 7.32-7.44 (m, 1 H) (s, 1 H) 7.51 – 7.63 (m, 1 H); LC/MS (M+H) = 298 (100%), 300 (98.5%). (2S,4S): 1 H NMR (400 MHz, CHLOROFORM-c/) delta ppm 1.22 (d, J=6.2 Hz, 3 H) 2.05 (dd, J=14.5, 10.7 Hz, 1 H) 2.25-2.44 (m, 1 H) 2.49 – 2.63 (m, 2 H) 3.44 – 3.59 (m, 2H) 3.86 – 3.99 (m, 1 H) 7.02 – 7.13 (m, 1 H) 7.19-7.31 (m, 1 H) (s, 1 H) 7.53-7.64 (m, 1 H); LC/MS (M+H) = 298 (100%), 300 (98.5%).
The synthetic route of 874285-03-7 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; PFIZER INC.; WO2009/69044; (2009); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts