6-tert-Butyl-m-cresol → 5-tert-Butyl-4-hydroxy-2-methylbenzaldehyde

温度

5 °C

Chlorobenzene (100 mL) and 2-tert-butyl-5-methylphenol (20.6 gm, 125 mmol) were combined and the mixture stirred and cooled to 5° C. Titanium tetrachloride (27.5 mL) and dichloromethyl methyl ether (19 mL, 210 mmol) were added separately and simultaneously over 45 minutes while holding the reaction temperature between 4 and 7° C. The resulting mixture was stirred at 0-5° C. for 3 hours. Water (100 mL) was cautiously added over 18 minutes to the reaction mixture while holding the temperature below 14° C. The mixture was extracted with ethyl acetate (200 mL) and the resulting organic layer was extracted with 12% hydrochloric acid (2×75 mL). The combined aqueous acid layers were diluted with water (50 mL) and back extracted with ethyl acetate (100 mL). This extract was combined with the first ethyl acetate extract and the whole extracted with 15% KOH (3×100 mL). The KOH extracts were combined and the pH adjusted to 3 with 37% hydrochloric acid (62.8 gm). The resulting mixture was extracted with 1:1 ethyl acetate/toluene (2×150 mL). These organic extracts were combined and back extracted with water (2×50 mL) and the organic solution concentrated to approximately 75 mL. 5-tert-Butyl-4-hydroxy-2-methylbenzaldehyde seed crystals were added and the mixture stirred and cooled to 25° C. The mixture was filtered and the product washed with toluene (30 mL) and vacuum dried at 40° C. to give 5-tert-butyl-4-hydroxy-2-methylbenzaldehyde (1): 15 g (78 mmol, 62%): mp: 168-170° C.

1. customthe reaction temperature between 4 and 7° C
2. stirringThe resulting mixture was stirred at 0-5° C. for 3 hours
3. customthe temperature below 14° C
4. extractionThe mixture was extracted with ethyl acetate (200 mL)
5. extractionthe resulting organic layer was extracted with 12% hydrochloric acid (2×75 mL)
6. additionThe combined aqueous acid layers were diluted with water (50 mL)
7. extractionback extracted with ethyl acetate (100 mL)
8. extractionextract
9. extractionthe whole extracted with 15% KOH (3×100 mL)
10. extractionThe resulting mixture was extracted with 1:1 ethyl acetate/toluene (2×150 mL)
11. extractionback extracted with water (2×50 mL)
12. concentrationthe organic solution concentrated to approximately 75 mL
13. addition5-tert-Butyl-4-hydroxy-2-methylbenzaldehyde seed crystals were added
14. stirringthe mixture stirred
15. temperaturecooled to 25° C
16. filtrationThe mixture was filtered
17. washthe product washed with toluene (30 mL) and vacuum
18. customdried at 40° C.

ORDレコード

ord-dc5ca3b8c1da46b8bbb7066813cf4476

出典データセット

uspto-grants-2002_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06380400B1