3-Buten-2-ol → HCID 13005705, compound

Temperature

2.5 °C

A reactor was charged with tetrabutylammonium hydrogen sulfate (0.17 Wt, 0.10 eq) and toluene (2.6 Wt, 3.0 V). The mixture was stirred and cooled to 0-5° C. While maintaining the internal temperature below 10° C., 50 wt % aqueous sodium hydroxide (4.5 wt, 3.0 V, 10.5 eq; 50% wt sodium hydroxide made from 2.25 wt of sodium hydroxide and 2.25 wt of water) was added, followed by 3-buten-2-ol (0.45 Wt, 0.53 V, 1.20 eq). The mixture was stirred at 0-10° C. for 15 minutes. tert-Butyl bromoacetate (1.0 Wt, 1.00 eq) was added while maintaining the internal temperature between 0-10° C. After the addition, the mixture was stirred between 0-5° C. for 1 h and monitored for complete consumption of tert-butyl bromoacetate (target >98% conversion). The reactor was charged with water (3.0 Wt, 3.0 V) and MTBE (4.4 Wt, 6.00 V) and warmed to 20-25° C. The biphasic mixture was stirred vigorously for 15 minutes, and then allowed to partition. The organic layer was washed with water (1.5 Wt, 1.5 V). The organic layer was concentrated under reduced pressure (T<40° C. and not less than 15 torr or 20 mbar). Heptane (1.0 wts, 1.5 V) and MTBE (1.1 wts, 1.5 V) were added. The solution was filtered to remove particulates, and rinsed with additional heptane:MTBE as necessary to clear the product. The solution was returned to the reactor and concentrated under reduced pressure to give 6 (0.91 Wt, 95.0%) as an oil with less than 1 volume of solvent.

1. additionwas added
2. stirringThe mixture was stirred at 0-10° C. for 15 minutes
3. temperaturewhile maintaining the internal temperature between 0-10° C
4. additionAfter the addition
5. stirringthe mixture was stirred between 0-5° C. for 1 h
6. custommonitored for complete consumption of tert-butyl bromoacetate (target >98% conversion)
7. additionThe reactor was charged with water (3.0 Wt, 3.0 V) and MTBE (4.4 Wt, 6.00 V)
8. temperaturewarmed to 20-25° C
9. stirringThe biphasic mixture was stirred vigorously for 15 minutes
10. customto partition
11. washThe organic layer was washed with water (1.5 Wt, 1.5 V)
12. concentrationThe organic layer was concentrated under reduced pressure (T<40° C. and not less than 15 torr or 20 mbar)
13. additionHeptane (1.0 wts, 1.5 V) and MTBE (1.1 wts, 1.5 V) were added
14. filtrationThe solution was filtered
15. customto remove particulates
16. washrinsed with additional heptane
17. concentrationconcentrated under reduced pressure
18. customto give 6 (0.91 Wt, 95.0%) as an oil with less than 1 volume of solvent

ORD record

ord-45615deb32724af38a0ddc80c61a658d

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962858B2