Hydrochloric Acid → 6-Chloro-7-hydroxychroman-4-carboxylic acid

A 20-liter 4-neck round-bottom flask was charged with glacial acetic acid (2.04 L), 6-chloro-4,7-bis(trimethylsilyloxy)chroman-4-carbonitrile (2.2 kg, 5.94 mol), and tin(II) chloride dihydrate (3.35 kg, 14.85 mol) and the resulting mixture was stirred at ambient temperature. Concentrated hydrochloric acid (5.0 L, 60 mol) was added, and the resulting mixture was stirred and heated to 80-85° C. for 12 hours. The reaction mixture was cooled to ambient temperature and water (3.6 L) was added, and stirring was continued at ambient temperature for 15 minutes. Isopropyl acetate (11.5 L) and water (5.8 L) were added, and stirring was continued at ambient temperature for 15 minutes. The layers were separated, and the aqueous layer was extracted with isopropyl acetate (2×2 L). The organic layers were combined and washed with brine (3×6 L), then dried over sodium sulfate and concentrated under reduced pressure at a temperature below 50° C. to afford crude 6-chloro-7-hydroxychroman-4-carboxylic acid as a brown semi-solid (1.70 kg, 125% yield).

1. stirringthe resulting mixture was stirred
2. temperatureheated to 80-85° C. for 12 hours
3. temperatureThe reaction mixture was cooled to ambient temperature
4. stirringstirring
5. stirringstirring
6. waitwas continued at ambient temperature for 15 minutes
7. customThe layers were separated
8. extractionthe aqueous layer was extracted with isopropyl acetate (2×2 L)
9. washwashed with brine (3×6 L)
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated under reduced pressure at a temperature below 50° C.

ORD record

ord-94ced5ac04c540efadb0c0ec6cc1c29b

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716498B2