Reference of 394-35-4, A common heterocyclic compound, 394-35-4, name is Methyl 2-fluorobenzoate, molecular formula is C8H7FO2, 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.
To a reactor under nitrogen atmosphere was added a toluene solution of ester 6 (LOO Wt, 1.0 eq), methyl 2-fluorobenzoate (0.91 Wt, 0.75 Vol 1.10 eq)5 and THF (0.53 Wt, 1.8 Vol). The solution was cooled to below -70 C. Lithium hexamethyldisilazide (LiHMDS, 1.0M in THF, 7.6 Wt, 8.6 Vol, 1,6 eq) was added at such rate that the internal temperature does not exceed -60°C.. After completion of the LiHMDS addition, the mixture was warmed (rate between 10-20C/h) and stirred at -40C for 1h. The reaction was monitored by GC (Conversion Target >95percent). If after 4h the conversion is still under targeted amount, additional LiHMDS 1M in THF was added (1.1 eq based on unreacted starting material). After achieving the target conversion, the internal temperature was raised (rate between 20-30°C/h) to 15 to 20 °C. 25 wtpercent aqueous ammonium chloride (1,7 Wt, 1.6 Vol) was added to the reactor keeping the internal temperature below 0 °C Upon completion of the addition, the mixture was warmed to ?0°C, and transferred to a vessel containing 25 wtpercent aqueous ammonium chloride (4.4 Wt, 4.1 Vol) and water (1.1 Wt, 1.1 Vol).The mixture was stirred for at least 30 min at 20-25 °C. The lower aqueous layer was removedand the organic layer was washed with 20 wt percent aqueous sodium chloride (3.0 Wt, 1.4 Vol). The mixture was stirred for at least 15 minutes then allowed to settle. The lower aqueous layer was removed. The organic phase was concentrated under reduce pressure (Jacket < 25 °C) untildistillation ceases. Toluene (6.6 Wt, 6.7 Vol) was added and the resulting mixture was washedwith water (3.0 Wt, 3.0 Vol), stirred for at least 15 min, then allowed to settle. The organics werewashed with water (3.0 Wt, 3.0 Vol) until pH is constant at pH=78. The organic phase was washed with 20percent aqueous sodium chloride (3.0 Wt, 1.4 Vol). The organic phase was concentrated under reduced pressure (jacket <25°C) to afford ketoester 11 (2.1 Wt) as an orangeoil.
The synthetic route of 394-35-4 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; ???????????????????????????; ? Buranko; Kimu ?; Chan ?; ?; Yoshizawa Kazuhiro; (94 pag.)JP2016/121177; (2016); A;,
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