Hydrogen Bromide → 3-(1H-pyrazol-1-ylmethyl)tricyclo[3.3.1.13,7]decane-1-thiol

Temperature

100 °C

A solution of EXAMPLE 26A (2.0 g) and thiourea (2.0 g) in a solvent mixture of acetic acid (20 mL) and 48% aqueous HBr solution (10 mL) was heated to 100° C. for 24 hours. The reaction was concentrated to dryness, and the residue was dissolved in 20% v/v ethanol in water (100 mL). Solid sodium hydroxide (10 g) was added, and the mixture was stirred overnight. The solution was acidified to pH 1 with concentrated HCl solution, and diluted with ethyl acetate (100 mL). The layers were separated, and the aqueous layer was extracted with additional ethyl acetate (2×100 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 10-50% ethyl acetate in hexane, to give the title product.

1. concentrationThe reaction was concentrated to dryness
2. dissolutionthe residue was dissolved in 20% v/v ethanol in water (100 mL)
3. additionSolid sodium hydroxide (10 g) was added
4. additiondiluted with ethyl acetate (100 mL)
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with additional ethyl acetate (2×100 mL)
7. washThe combined organic layers were washed with water
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by silica gel chromatography
12. washeluting with a gradient of 10-50% ethyl acetate in hexane

ORD record

ord-2c27fcecd36a4ba793bed4d123e64bab

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889675B2