Hydrochloric Acid → Z-2,2-dimethyl-5-carboxymethylene-1,3-dioxolan-4-one

Temperature

-40 °C

A stirred solution of tartaric acid bis(acetonide) prepared as in Example 1 (1.0 kg) in tetrahydrofuran (5.0 L) was cooled to −40° C. A chilled 0.75 M solution of potassium tert-butoxide in tetrahydrofuran (7.0 L) was added and stirring was continued for 15 min at −40° C. In a separate reactor, a 1.2 M solution of HCl was generated by reaction of acetyl chloride (0.50 L) with methanol (0.31 L) in tetrahydrofuran (5.0 L) 0-5° C. The original reaction is quenched by addition of the chilled HCl solution. The mixture was allowed to warm to room temperature with stirring over the course of 1 h, after which the THF content was reduced to <2% by vacuum distillation. Ethyl acetate (20 L) was added and the mixture was concentrated to 10 L. Deionized water (8.0 L) was added and the pH was adjusted to <2.5 with 1 N HCl. The organic phase was separated and the aqueous phase was further extracted with ethyl acetate (5.0 L). The combined organics were concentrated to a volume of 3 L by vacuum distillation whereupon heptane (6.0 L) was added. The product mixture was vigorously agitated at 15° C. for 1 h after which the crystalline product was collected by filtration and washed with heptane (2×2.0 L). Vacuum drying at 50° C. afforded Z-2,2-dimethyl-5-carboxymethylene-1,3-dioxolan-4-one (577 g, 77%) as fine white needles. NMR and HPLC analysis indicated the product purity was 100%.

1. customThe original reaction
2. customis quenched by addition of the chilled HCl solution
3. temperatureto warm to room temperature
4. stirringwith stirring over the course of 1 h
5. distillationafter which the THF content was reduced to <2% by vacuum distillation
6. additionEthyl acetate (20 L) was added
7. concentrationthe mixture was concentrated to 10 L
8. additionDeionized water (8.0 L) was added
9. customThe organic phase was separated
10. extractionthe aqueous phase was further extracted with ethyl acetate (5.0 L)
11. concentrationThe combined organics were concentrated to a volume of 3 L by vacuum distillation whereupon heptane (6.0 L)
12. additionwas added
13. stirringThe product mixture was vigorously agitated at 15° C. for 1 h after which the crystalline product
14. filtrationwas collected by filtration
15. washwashed with heptane (2×2.0 L)
16. customVacuum drying at 50° C.

ORD record

ord-01d33214b8dd4c1d85bcbe17385246a6

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07507838B2