Acetone → Benzeneacetic acid, 4-(difluoromethoxy)-α-(1-methylethyl)-, methyl ester, (-)-

Temperature

30 °C

A mixture of methyl 2-(4-hydroxyphenyl)-3-methylbutyrate (44.42 g of 93.8% pure material=41.67 g; 0.20 mol), acetone (83.3 ml), 2-propanol (83.3 ml), and water (62.8 ml) is stirred at 30° C. in a closed system. After the system is evacuated, chlorodifluoromethane is introduced into the reaction mixture under a pressure of 0.49 kg cm-2. After about 5 minutes, one equivalent of 50.6% of aqueous sodium hydroxide (10.4 ml; 0.2 mol) from a pressurized reservoir is added all at once causing the reaction mixture to exotherm to 34° C. with a concomitant rise in pressure to 0.7 kg cm-2. Slow addition of the rest of 50.6% aqueous sodium hydroxide (31.6 ml; 0.60 mol) then commences and is completed in about 60 minutes. About 5 minutes after the beginning of the slow addition of the base, the pressure under which the chlorodifluoromethane is introduced into the reaction mixture is increased to 1.05 kg cm-2. In about 45 minutes a total of 0.60 mol of chlorodifluoromethane (51.66 g) is added. After the addition of the sodium hydroxide is completed, the reaction mixture is stirred for an additional hour. The system is then evacuated to remove any unreacted chlorodifluoromethane from the reaction mixture. Next, a 1:1 mixture (by volume) of acetone:2-propanol (100 ml) is added while washing down the reactor. The reaction mixture is filtered and the organic layer is separated yielding 334.6 g of an orange liquid.

1. customAfter the system is evacuated
2. additionchlorodifluoromethane is introduced into the reaction mixture under a pressure of 0.49 kg cm-2
3. customto exotherm to 34° C. with a concomitant rise in pressure to 0.7 kg cm-2
4. waitcommences and is completed in about 60 minutes
5. additionAbout 5 minutes after the beginning of the slow addition of the base
6. temperatureis increased to 1.05 kg cm-2
7. stirringthe reaction mixture is stirred for an additional hour
8. customThe system is then evacuated
9. customto remove any unreacted chlorodifluoromethane from the reaction mixture
10. additionNext, a 1:1 mixture (by volume) of acetone:2-propanol (100 ml) is added
11. washwhile washing down the reactor
12. filtrationThe reaction mixture is filtered
13. customthe organic layer is separated

ORD record

ord-b7d6c9277a504637a7b2b4cb327a3466

Source dataset

uspto-grants-1983_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04405529