Water → Methyl 6-(difluoromethoxy)nicotinate

A mixture of commercially available methyl 6-hydroxynicotinate (3.000 g; 19.59 mmol) in anh. MeCN (320 ml) was treated portionwise with NaH (60% dispersion in mineral oil; 2.115 g; 52.89 mmol), and stirring at rt, under nitrogen, was continued for 20 min. FSO2CF2CO2H (5.931 g; 33.30 mmol) was then added dropwise, and the resulting heterogeneous mixture was further stirred at rt, under nitrogen, for 30 min. Water (10 ml) was slowly added, and acetonitrile was removed under reduced pressure. Water (150 ml) and AcOEt (150 ml) were added, and the separated aq. layer was further extracted with AcOEt (2×100 ml). The mixed organic layers were washed with brine (100 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM) afforded methyl 6-(difluoromethoxy)nicotinate as a beige solid. LC-MS (conditions D): tR=0.93 min.; no ionisation.

1. stirringthe resulting heterogeneous mixture was further stirred at rt, under nitrogen, for 30 min
2. customacetonitrile was removed under reduced pressure
3. additionWater (150 ml) and AcOEt (150 ml) were added
4. extractionthe separated aq. layer was further extracted with AcOEt (2×100 ml)
5. washThe mixed organic layers were washed with brine (100 ml)
6. dry with materialdried over anh. MgSO4
7. filtrationfiltered
8. concentrationconcentrated to dryness under reduced pressure
9. customPurification by FC (DCM)

ORD-Eintrag

ord-6ec6e06f45ea4f31ad13720f982fe0dc

Quelldatensatz

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09242970B2