Sodium Carbonate → Benzyl 2-(difluoromethoxy)acetate

Temperatur

45 °C

Benzyl 2-hydroxyacetate (3.2 ml, 22.2 mmol), sodium sulfate (0.63 g, 4.4 mmol), and MeCN (34 ml) were placed in a 100 ml two-necked RBF fitted with a magnetic stirrer, a dropping funnel and a refluxing condenser. 2,2-Difluoro-2-(fluorosulfonyl)acetic acid (9.18 ml, 89 mmol) was then added with stirring at 45° C. After addition, the mixture was further stirred for 1 h at this temperature. The reaction mixture was poured into 10% aqueous sodium carbonate and was extracted with diethyl ether, the combined extracts were washed with 10% aqueous sodium carbonate, water, brine, dried over sodium sulfate, and concentrated. The crude material was purified by column chromatography (4:1 Hexanes/EtOAc) to afford the intermediate benzyl 2-(difluoromethoxy)acetate which was dissolved in EtOAc (34 mL). N-Ethyl-N-isopropylpropan-2-amine (0.561 ml, 3.2 mmol) was added and after degassing with nitrogen, palladium on carbon (0.680 g, 0.64 mmol) was added. The reaction was purged with hydrogen and stirred under 50 PSI of hydrogen for 24 hours. The degassed reaction was filtered through a pad of Celite and concentrate to afford the titled product as the amine salt which was used directly for subsequent reaction steps without further purification.

1. customfitted with a magnetic stirrer, a dropping funnel and a refluxing condenser
2. additionAfter addition
3. stirringthe mixture was further stirred for 1 h at this temperature
4. extractionwas extracted with diethyl ether
5. washthe combined extracts were washed with 10% aqueous sodium carbonate, water, brine
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated
8. customThe crude material was purified by column chromatography (4:1 Hexanes/EtOAc)

ORD-Eintrag

ord-80212c1c70e94680b6640921b565c30e

Quelldatensatz

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08552181B2