Hydrochloric Acid → HCID 66712386, compound

To (1R,2S)-2-((R)-2′-cyclopentyl-2′-hydroxy 2′-phenylacetoxy)-7-(tert-butoxycarbonyl)-7-azabicyclo[2.2.1]heptane (76 mg, 0.182 mmol) was added 1 mL of 4N hydrochloric acid in dioxane and the mixture was stirred at room temperature for 0.5 hr. The dioxane was removed under vacuum and the residue was basified with ammonium hydroxide to pH 10 and extracted with 3×30 mL of methylene chloride. The combined organic layers were dried over sodium sulfate and concentrated to yield the crude amine. To this amine, dissolved in 5 mL of dichloroethane, was added 0.1 mL of formaldehyde solution (37% w/v in water) followed by sodium triacetoxyborohydride (76 mg, 0.364 mmol) and the mixture stirred at room temperature overnight. Water was added and the mixture was extracted with 3×50 mL of methylene chloride. The combined organic layers were dried over sodium sulfate and concentrated to yield the crude tertiary amine which was further purified on silica gel using methylene chloride/methanol/ammonia (90:9:1) as the eluent to yield 46 mg of (1R,2S)-2-((R)-2′-cyclopentyl-2′-hydroxy 2′-phenylacetoxy)-7-methyl-7-azabicyclo[2,2,1]heptane as an oil.

1. customThe dioxane was removed under vacuum
2. extractionextracted with 3×30 mL of methylene chloride
3. dry with materialThe combined organic layers were dried over sodium sulfate
4. concentrationconcentrated
5. customto yield the crude amine
6. stirringthe mixture stirred at room temperature overnight
7. extractionthe mixture was extracted with 3×50 mL of methylene chloride
8. dry with materialThe combined organic layers were dried over sodium sulfate
9. concentrationconcentrated
10. customto yield the crude tertiary amine which
11. customwas further purified on silica gel

ORD record

ord-71f1de9bd5dc4d919ecff4d4604994c2

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09320731B2