Methanesulfonic Acid → 1,1-Dimethylethyl (4R,6R)-6-(cyanomethyl)-2,2-dimethyl-1,3-dioxane-4-acetate
Reaction equation
[C:1]([CH2:3][CH:4]([OH:16])[CH2:5][CH:6]([OH:15])[CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])#[N:2].CS(O)(=O)=O.CO[C:24](OC)([CH3:26])[CH3:25]>>[C:1]([CH2:3][C@H:4]1[O:16][C:24]([CH3:26])([CH3:25])[O:15][C@@H:6]([CH2:7][C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[CH2:5]1)#[N:2]Participants
4
Procedure
Crude [R—(R*,R*)]-1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate (about 150 moles) from Step (2) is diluted with 100 kg of 2,2-dimethoxypropane and acidified with about 1 L of methanesulfonic acid. The reaction is quenched by the addition of aqueous sodium bicarbonate solution and concentrated by vacuum distillation. The residue is diluted with 150 L of hexane, and the layers separated. The organic layer is washed with aqueous sodium bicarbonate solution and cooled to 0° C.±10° C. to crystallize. The product is collected by filtration and washed with cooled hexane, then dried affording 28.5 kg of (4R cis) 1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate.
Workup
- customThe reaction is quenched by the addition of aqueous sodium bicarbonate solution
- concentrationconcentrated by vacuum distillation
- additionThe residue is diluted with 150 L of hexane
- customthe layers separated
- washThe organic layer is washed with aqueous sodium bicarbonate solution
- temperaturecooled to 0° C.±10° C.
- customto crystallize
- filtrationThe product is collected by filtration
- washwashed with cooled hexane
- customdried
Sources & evidence
- ORD record
- ord-d4e02e5c8a004da38c85d72f2d268a42
- Source dataset
- uspto-grants-2005_11
- Patent number
- US06962994B2
Reaction notes
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