Isopropyl Acetate → HCID 59800152, compound

Temperature

2.5 °C

194 g 3-nitro-benzenesulfonyl chloride (1.13 equiv.) were charged in the reaction vessel followed by 1.3 l isopropyl acetate and the solution was cooled to 0-5° C. A solution of 65 g 2,2-difluoroethanol (753 mmol, 1 equiv.), 163 ml triethylamine (1.55 equiv.) and 325 ml isopropyl acetate was added dropwise over 30 min, keeping the temperature between 0-5° C. After 4 h reaction (HPLC in process control), the reaction mixture was washed with 650 ml water. The water phase was re-extracted with 650 ml isopropyl acetate. The organic phases were washed with 650 ml 1M HClaq and 650 ml 10% NaClaq solution. The organic phases were combined, dried over MgSO4, filtered and concentrated to dryness under reduced pressure to give 196 g 2,2-difluoroethyl 3-nitrobenzenesulfonate (97% yield) as a viscous oil which crystallized on standing. The product can also be crystallized from isopropanol (seeding at 30° C., concentration: ca 13 L/kg product).

1. custombetween 0-5° C
2. customAfter 4 h reaction (HPLC in process control)
3. washthe reaction mixture was washed with 650 ml water
4. extractionThe water phase was re-extracted with 650 ml isopropyl acetate
5. washThe organic phases were washed with 650 ml 1M HClaq and 650 ml 10% NaClaq solution
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated to dryness under reduced pressure

ORD record

ord-37bceaedd4e74e2999f23dbd7c95c98f

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07872141B2