Hydrochloric Acid → Methyl 6-chloro-2,2-dimethylchroman-8-carboxylate

Temperature

10 °C

To a solution of methyl 2,2-dimethyl-3,4-dihydro-2H-chromene-8-carboxylate (330 mg, 1.50 mmol) in dichloromethane (3.74 mL) and methanol (3.74 mL) was added concentrated HCl (61.5 μL, 0.75 mmol) at 10° C. NCS (206 mg, 1.54 mmol) as added portion-wise. The solution was stirred for 1 hour at 8-12° C. The solution was then poured into a mixture of water (5.00 mL), saturated aqueous sodium thiosulfate (5.00 mL), 1 N aqueous NaOH (5.00 mL) and dichloromethane (30.0 mL). The mixture was stirred for 15 minutes at room temperature and the two phases were separated. The organic phase was acidified to pH<2 with 1 N aqueous HCl. The mixture was then extracted with dichloromethane (10.0 mL, 2×). The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The crude residue was purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes to give the desired product as a colorless oil.

1. stirringThe mixture was stirred for 15 minutes at room temperature
2. customthe two phases were separated
3. extractionThe mixture was then extracted with dichloromethane (10.0 mL, 2×)
4. dry with materialThe combined organic layers were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under vacuum
7. customThe crude residue was purified by silica gel chromatography
8. washeluting with 0-15% EtOAc/hexanes

ORD record

ord-a20f0fe3bbda415b8f40a4c89e217936

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08742110B2