Lithium Hydroxide → (2s, 4r)-2-Benzoyloxymethyl-1,3-dioxolane-4-carboxylic acid
Reaction equation
C[O:2][C:3]([C@H:5]1[CH2:9][O:8][CH:7]([CH2:10][O:11][C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[O:6]1)=[O:4].O1CCCC1.[OH-].[Li+]>O>[C:12]([O:11][CH2:10][C@@H:7]1[O:6][C@@H:5]([C:3]([OH:4])=[O:2])[CH2:9][O:8]1)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1Participants
Procedure
To a solution of methyl-2-(R,S)-benzoyloxymethyl-1,3-dioxolane-4-(R)-carboxylate (III), (411 g, 1.54 mmol, 1 eq., 2:1 mixture of cis and trans isomers) in a 1:1 mixture of tetrahydrofuran (THF) and water, lithium hydroxide (LiOH) (64.8 g, 1.54 moles, 1 eq) was added portion wise 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 (IVa) (56.5%) and 116 g of the trans isomer (IVb) (30%). Each of isomers was independently used for next step.
Workup
- additionwas added portion wise over a period of 30 min.
- customthe reaction flask temperature below 30° C
- customTHF was removed by vacuum
- additionthe aqueous solution was acidified to pH=2.5-3.2, by dropwise addition of 30% (w/w) sulphuric acid
- extractionThe resulting solution was extracted with dichloromethane (4×400 mL)
- washThe combined organic phase was washed with brine
- dry with materialdried over sodium sulphate
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-af738ee80cee4bd58ad093f4b75f88fd
- Source dataset
- uspto-grants-2003_05
- Patent number
- US06566365B1
Reaction notes
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