1,2-Dibromoethane → methyl 3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

Temperature

70 °C

To a 2000 ml three-necked flask under N2 containing 3-Amino-4-hydroxy-benzoic acid methyl ester (31.35 g, 187 mmol) in anhydrous DMF (630 ml; 20 vols) at RT, was added K2CO3 (103 g, 4 eq.) in one portion followed by 1,2dibromoethane (65 ml, 4 eq.) in one portion. The reaction mixture was stirred at 70° C. for 12 h. Temperature was allowed to cool down to RT, and HCl1N was added until pH=8, and extraction was performed using diethyl ether (3*200 ml). The organic phase was washed with water (2*200 ml) and dried over MgSO4 and concentrated to afford a brown red oil with solid, which was taken up again in diethyl ether (450 ml) and THF (50 ml) and filtered to remove a white solid. To the filtrate was added HCl1N, and diethyl ether (130 ml) was added, suspension was stirred at RT for 5 minutes and filtered to give 27.6 g of crude product. The aqueous phases were again extracted with ethyl acetate to afford additional 6.23 g of product. The combined fractions (32 g) were recrystallised from EtOH (420 ml; 13 vols) to give after filtration and drying a white powder (19.47 g (16.37 g free base)), yield=40%.

1. temperatureto cool down to RT
2. additionHCl1N was added until pH=8, and extraction
3. washThe organic phase was washed with water (2*200 ml)
4. dry with materialdried over MgSO4
5. concentrationconcentrated
6. customto afford a brown red oil with solid, which
7. filtrationTHF (50 ml) and filtered
8. customto remove a white solid
9. additionTo the filtrate was added HCl1N, and diethyl ether (130 ml)
10. additionwas added
11. stirringsuspension was stirred at RT for 5 minutes
12. filtrationfiltered
13. customto give 27.6 g of crude product
14. extractionThe aqueous phases were again extracted with ethyl acetate

ORD record

ord-445cd444c7e44dfd87c4e047d77e1a05

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07846925B2