Hydrochloric Acid → HCID 86674112, compound

A solution of (R)—N2-(bis(4-methoxyphenyl)(phenyl)methyl)-N6′-(diphenylmethylene)-5,5-difluoro-5,6-dihydrospiro[[1,3]oxazine-4,4′-thiochroman]-2,6′-diamine (613 mg, 815 μmol) in dichloromethane (10 ml) was treated with trifluoroacetic acid (930 mg, 8.15 mmol). The orange colored solution was stirred at room temperature for 15 hours. Thereafter, the reaction mixture was diluted with dichloromethane (10 ml) and washed with a 1M-solution of sodium carbonate (5 ml). The organic layer was separated, dried over sodium sulphate and evaporated. The resulting yellow oil was dissolved in dioxane (8 ml), then hydrochloric acid (4N in dioxane, 2.04 ml) was added dropwise. A precipitate was formed, which dissolved after addition of hydrochloric acid (4N in dioxane, 2.0 ml). The orange colored solution was stirred at room temperature for 15 hours. For the workup, the solution was evaporated at reduced pressure and the residue dissolved in ethyl acetate (30 ml). The organic layer was washed with hydrochloric acid (1N, 8 ml), the aqueous layer was separated and adjusted to pH 9 by addition of sodium hydroxide (2N). Thereafter, the aqueous layer was extracted with ethyl acetate (3×30 ml), the organic layers combined and dried over sodium sulphate. After evaporation at reduced pressure, the (R)-5,5-difluoro-5,6-dihydro spiro[[1,3]oxazine-4,4′-thiochroman]-2,6′-diamine (230 mg, 89% yield) was obtained as a yellow solid pure enough to be used in the next step without further purification. MS (ISP): m/z=286.1 [M+H]+.

1. washwashed with a 1M-solution of sodium carbonate (5 ml)
2. customThe organic layer was separated
3. dry with materialdried over sodium sulphate
4. customevaporated
5. dissolutionThe resulting yellow oil was dissolved in dioxane (8 ml)
6. additionhydrochloric acid (4N in dioxane, 2.04 ml) was added dropwise
7. customA precipitate was formed
8. dissolutionwhich dissolved
9. stirringThe orange colored solution was stirred at room temperature for 15 hours
10. customFor the workup, the solution was evaporated at reduced pressure
11. dissolutionthe residue dissolved in ethyl acetate (30 ml)
12. washThe organic layer was washed with hydrochloric acid (1N, 8 ml)
13. customthe aqueous layer was separated
14. additionadjusted to pH 9 by addition of sodium hydroxide (2N)
15. extractionThereafter, the aqueous layer was extracted with ethyl acetate (3×30 ml)
16. dry with materialdried over sodium sulphate
17. customAfter evaporation at reduced pressure

ORD record

ord-733b2811fb2041cc990d68ad1b23d88e

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09079919B2