Butanal → HCID 69465141, compound

A solution of N-propionyl-2-benzoxazolone (100.0 g) in anhydrous CH2Cl2 (1100 mL) was cooled to 3° C. with mechanical stirring under N2 atmosphere. TiCl4 (58.4 mL) was added at a rate such that the internal temperature remained below 10° C. (ca. 10 minutes). The resulting yellow slurry was stirred vigorously for 40 minutes, then triethylamine (87.4 mL) was added at a rate such that the internal temperature remained below 10° C. (ca. 10 minutes). The resulting deep red solution was stirred for 80 minutes. Butyraldehyde (58.9 mL) was added at a rate such that the internal temperature remained below 10° C. (ca. 20 minutes), and the reaction was followed by thin-layer chromatography (4:1 hexanes/ethyl acetate). After stirring for 90 minutes, the reaction was quenched by addition of 450 mL of 2 N HCl. The phases were separated, and the aqueous phase was extracted 3 times with 750-mL portions of ether. The organic phases were combined and washed three times with 200-mL portions of 2 N HCl. The acidic washes were combined and back-extracted 3 times with 150-mL portions of ether. The combined organic extract was washed once with 300 mL of sat. aq. NaHCO3, and once with 300 mL of sat. aq. NaCl. The organic phase was then dried over MgSO4, filtered, and concentrated under vacuum to a yellow slurry. The product was collected by vacuum filtration and rinsed with hexanes to yield a colorless solid. Concentration of the filtrate yielded a second crop of product, which was collected in the same manner, giving a combined 103 g (80% yield) of crystalline product; mp=123-4° C. The mother liquor can be chromatographed (4:1 hexanes/ethyl acetate) to yield additional product. 1H-NMR (CDCl3, 400 MHz): δ 8.10 (1H, m), 7.23-7.32 (3H, m), 4.12 (1H, m), 3.98 (1H, dq, J=3,7), 2.26 (1H, br s), 1.38-1.64 (4H, m), 1.34 (3H, d, J=7), 0.98 (3H, t, J=7). 13C-NMR (CDCl3, 100 MHz): δ 176.4, 151.1, 142.2, 127.8, 125.5, 124.9, 116.3, 109.9, 71.3, 43.7, 36.2, 19.2, 13.9, 10.1.

1. customremained below 10° C.
2. custom(ca. 10 minutes)
3. stirringThe resulting yellow slurry was stirred vigorously for 40 minutes
4. customremained below 10° C.
5. custom(ca. 10 minutes)
6. stirringThe resulting deep red solution was stirred for 80 minutes
7. customremained below 10° C.
8. custom(ca. 20 minutes)
9. stirringAfter stirring for 90 minutes
10. customthe reaction was quenched by addition of 450 mL of 2 N HCl
11. customThe phases were separated
12. extractionthe aqueous phase was extracted 3 times with 750-mL portions of ether
13. washwashed three times with 200-mL portions of 2 N HCl
14. extractionback-extracted 3 times with 150-mL portions of ether
15. extractionThe combined organic extract
16. washwas washed once with 300 mL of sat. aq. NaHCO3
17. dry with materialThe organic phase was then dried over MgSO4
18. filtrationfiltered
19. concentrationconcentrated under vacuum to a yellow slurry
20. filtrationThe product was collected by vacuum filtration
21. washrinsed with hexanes
22. customto yield a colorless solid
23. customConcentration of the filtrate yielded a second crop of product, which
24. customwas collected in the same manner

ORD record

ord-8917a6457d684d8c96cf56f756eb00bb

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06492562B1