Lithium Hydroxide → (2s, 4r)-2-Benzoyloxymethyl-1,3-dioxolane-4-carboxylic acid

To a solution of methyl-2-(R,S)-benzoyloxymethyl-1,3-dioxolane-4-(R)-carboxylate, (411 g, 1.54 mmol, 1 eq. , 2:1 mixture of cis and trans isomers) in a 1:1 mixture of THF and water, lithium hydroxide (64.8 g, 1.54 moles, 1 eq) was added portionwise over a period of 30 min., keeping the reaction flask temperature below 30° C. After 90 min., THF was removed by vacuum and the aqueous solution was acidified to pH 2.5-3.2, by dropwise addition of 30% (w/w) sulphuric acid. The resulting solution was extracted with dichloromethane (4×400 mL). The combined organic phase was washed with brine, dried over sodium sulphate and concentrated to produce 380 g of a dark oil. The isomers were separated by column chromatography on silica gel, using 2% acetic acid in dichloromethane to produce 220 g of the cis isomer (56.5%) and 116 g of the trans isomer (30%). Each of isomers was independently used for next step.

1. additionwas added portionwise over a period of 30 min.
2. customthe reaction flask temperature below 30° C
3. customTHF was removed by vacuum
4. additionthe aqueous solution was acidified to pH 2.5-3.2, by dropwise addition of 30% (w/w) sulphuric acid
5. extractionThe resulting solution was extracted with dichloromethane (4×400 mL)
6. washThe combined organic phase was washed with brine
7. dry with materialdried over sodium sulphate
8. concentrationconcentrated

ORD record

ord-ae1f8c9d88154583a5f99e01b202596f

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06358963B1