Ethyl bromoacetate → HCID 10755331, compound

854.0 g of 1-(1-ethoxyethoxy)-3-methoxybenzene (content: 717.4 g (3.66 mol)) was put into a 20 L reactor under a nitrogen atmosphere and rinsed in with 7174 mL of tetrahydrofuran and the mixture was stirred. A coolant which was set to 4° C. was circulated through the jacket of the reactor and 1156 g (4.41 mol) of n-butyllithium [2.71 M, n-hexane solution] was added dropwise for 41 minutes, and the reaction mixture was stirred at the same temperature for about 1.5 hours. The coolant temperature was set to −20° C., and after it was confirmed that the mixture's temperature lowered below −10° C., 417.8 g (2.19 mol) of copper (I) iodide was added portionwise divided into three to the reaction mixture and the reaction mixture was stirred at the same temperature for about 14 hours. The coolant temperature was changed to −90° C. and 702.1 g (4.20 mol) of ethyl bromoacetate was added dropwise to the reaction mixture over 26 minutes and rinsed in with 10 mL of tetrahydrofuran. After the dropwise addition was completed, the reaction mixture was stirred for 44 minutes, and the liquid cooling temperature was changed to −35° C. and the reaction mixture was further stirred for about 1.8 hours. The coolant temperature was changed to −20° C., and the reaction mixture was stirred for one hour after the time point when temperature of the mixture exceeded −20° C. and progress of the reaction was confirmed by HPLC. 1435 mL of 28% ammonium hydroxide solution was added to the reaction mixture at the same temperature for about 30 minutes and the coolant temperature was changed to 25° C. The reaction mixture was added and extracted with 7174 mL of toluene and the organic layer was washed with 1440 mL of 28% ammonium hydroxide solution and 1435 mL×3 water sequentially. The obtained organic layer was added with 127 mL (0.73 mol) of N,N-diisopropylethylamine and concentrated in vacuo to afford a pale orange oil containing the title compound.

1. washrinsed in with 7174 mL of tetrahydrofuran
2. customwas set to 4° C.
3. additionwas added dropwise for 41 minutes
4. stirringthe reaction mixture was stirred at the same temperature for about 1.5 hours
5. customwas set to −20° C.
6. customlowered below −10° C.
7. stirringthe reaction mixture was stirred at the same temperature for about 14 hours
8. customwas changed to −90° C.
9. washrinsed in with 10 mL of tetrahydrofuran
10. additionAfter the dropwise addition
11. stirringthe reaction mixture was stirred for 44 minutes
12. temperaturethe liquid cooling temperature
13. customwas changed to −35° C.
14. stirringthe reaction mixture was further stirred for about 1.8 hours
15. customwas changed to −20° C.
16. stirringthe reaction mixture was stirred for one hour after the time point when temperature of the mixture
17. customexceeded −20° C.
18. addition1435 mL of 28% ammonium hydroxide solution was added to the reaction mixture at the same temperature for about 30 minutes
19. customwas changed to 25° C
20. additionThe reaction mixture was added
21. extractionextracted with 7174 mL of toluene
22. washthe organic layer was washed with 1440 mL of 28% ammonium hydroxide solution and 1435 mL×3 water sequentially
23. concentrationconcentrated in vacuo
24. customto afford a pale orange oil

ORD record

ord-b671bcd0beb146f98ce035c58a2e46e4

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08110688B2