Related Products of 60899-34-5,Some common heterocyclic compound, 60899-34-5, name is 1-Oxo-2,3-dihydro-1H-indene-4-carbonitrile, molecular formula is C10H7NO, 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.
A stirred mixture of 1 -oxo-2,3 -dihydro- 1 H-indene-4-carbonitrile (mt 1) (20.Og, 98 wt%, 18.6 assay g, 124.8 mmol) in abs EtOH (20 mL), triethylorthoformate (80 mL, 481 mmol) and methanesulfonic acid (0.88 mL, 12.5 mmol) in toluene (80 mL)was heated at 43 -47C. After 1 h, GC analysis showed orthoformate consumed and 12.8 area% of mt 1 remaining. A further charge of triethylorthoformate (20 mL, 120.2 mmol) was made and after 45 mm GC analysis showed 1.5 area% mt 1. The batch was cooled to ambient temperature and then poured into 1 M aq. K2HPO4 (200 mL) with vigorous stirring while maintaining a quench temperature < 15 C. The two-phasemixture was vigorously stirred for 10 mm. The phases were separated and the aqueous phase (pH 11) was back extracted with toluene (100 mL). The organic phases were combined and distilled at atmospheric pressure to remove 340 mL distillate. Toluene was added (500 mL) and distilled at atmospheric pressure to remove 500 mL distillate. Total distillation time 3 h, temperature range 80-120 C. At this point the batch wasstored overnight at < 5 C. Excess orthoformate was removed by chasing with ethyl acetate (100 mL) under reduced pressure until distillation stopped. Another volume of ethyl acetate (100 mL) was added and then concentrated under reduced pressure until distillation stopped. A third volume of ethyl acetate (100 mL) was added and then concentrated under reduced pressure until distillation stopped, after which GC analysisconfirmed no orthoformate remaining. The crude was then stirred at 110 C for 1 h, to convert the intermediate ketal to 3-ethoxy-1H-indene-7-carbonitrile (mt 2). Upon cooling, the crude (mobile oil, 21.34 g) was assayed for mt 2 by ?H NIVIR employing mesitylene as an internal standard. The oil assayed at 78.1 wt% product = 16.73 assay g, 90.0 mmol = 72.1 % assay yield. The crude oil was then purified by filtration througha silica gel plug eluting with 15% EtOAc/hexane. The pure fractions were combined and utilized for the next step. ?H NIVIR (400 MHz, d6-DMSO) 7.78 (d, J = 8.4, 1H), 7.63 (m, 1H), 7.49 (m, 1H), 5.60 (m, 1H), 1.38 (t, J= 6.8 Hz, 1H), 1.19 (t, J= 6.8 Hz, 1H); LRMS: calcd for C,2H,2NO [M + H]: 186.2; Found: 186.2.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Oxo-2,3-dihydro-1H-indene-4-carbonitrile, its application will become more common.
Reference:
Patent; CELGENE INTERNATIONAL II SARL; MEADOWS, Kristen, R., Taylor; SKOLNICK, Brett; DALVIE, Deepak; (78 pag.)WO2018/208855; (2018); A1;,
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