Acetic Anhydride → HCID 10773981, compound

Temperature

0 °C

In a 1-L, 3-neck r.b. flask with an addition funnel, a solution 5-chloro-2-pentanone (33.1 g, 274 mmol) in THF (140 mL) was treated with ethynylmagnesium bromide (564 mL of a 0.5 M solution in THF, 282 mmol, 1.03 equiv) over 0.5 h at -78° C. The internal temperature rose to -30° C. during the addition. The mixture was allowed to warm to 0° C. and stirred for 1 h, then was poured into a cold mixture of ether (400 mL) and 1 N NaHSO4 (400 mL). The aqueous layer was extracted with ether (2×200 mL), and the combined organic layers were washed with brine, dried (MgSO4) filtered, and concentrated to 42 g of a brown oil. This material was transferred to a 250-mL r.b. flask, whereupon pyridine (27 mL) and acetic anhydride (36.4 g, 356 mmol, 1.3 equiv) were added, then the flask was cooled to 0° C. DMAP (1.67 g, 13.7 mmol, 5%) was added, and the solution was stirred for 2 d, then treated with MeOH (10 mL). After 1 h, the solution was poured into a cold mixture of ether (250 mL) and 2 N NaHSO4 (250 mL). The aqueous layer was extracted with ether (250 mL), and the combined organic layers were washed with brine (250 mL), dried (MgSO4), filtered, and concentrated to a brown oil. Distillation afforded 30.5 g (58.8%) of Compound 2, a colorless oil, bp 79-80° C. @ 10 mm Hg. Data for Compound 2: 1H NMR (400 MHz, CDCl3) 3.52-3.65 (m, 2H), 2.57 (s, 1H), 1.85-2.15 (m, 4H), 2.04 (s, 3H), 1.71 (s, 3H).

1. additionThe internal temperature rose to -30° C. during the addition
2. extractionThe aqueous layer was extracted with ether (2×200 mL)
3. washthe combined organic layers were washed with brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated to 42 g of a brown oil
7. temperaturethe flask was cooled to 0° C
8. stirringthe solution was stirred for 2 d
9. waitAfter 1 h
10. extractionThe aqueous layer was extracted with ether (250 mL)
11. washthe combined organic layers were washed with brine (250 mL)
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated to a brown oil
15. distillationDistillation

ORD record

ord-839b2ae037924326adcabb41333309d8

Source dataset

uspto-grants-2000_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06017924