Benzyl Alcohol → HCID 86663454, compound

Temperature

60 °C

The compound (535 mg, 1.41 mmol) obtained in Example 61c was dissolved in a mixed solvent (6 mL) of tetrahydrofuran and methanol (1:1), a 1 N aqueous sodium hydroxide solution (1 mL) was added, and the mixture was stirred at 60° C. for 5 hours. After the reaction was completed, a 1 N aqueous hydrochloric acid solution (10 mL) was added to the reaction mixture under ice cooling, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in 1,4-dioxane (6 mL), diphenyl phosphate azide (0.238 mL, 1.10 mmol), triethylamine (0.154 mL, 1.10 mmol) and benzyl alcohol (0.228 mL, 2.21 mmol) were added under ice cooling, and the mixture was stirred at 100° C. under a nitrogen atmosphere for 16 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, the resulting crude benzyl (2-{3-([tert-butoxycarbonyl)(methyl)amino]propyl}-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)carbamate (354 mg, 0.757 mmol) was dissolved in N,N-dimethylformamide (7 mL), methyl iodide (0.236 mL, 3.79 mmol) and 55% sodium hydride (40 mg, 0.909 mmol) were added under ice cooling, and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After the reaction was completed, water was added to the reaction mixture under ice cooling, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate, 1:5, v/v) to give the title compound (320 mg; yield, 88%) as a colorless oily substance.

1. customto separate the layers
2. customThe resulting organic layer was separated
3. washwashed with saturated sodium chloride solution
4. dry with materialdried with anhydrous sodium sulfate
5. customthe solvent was evaporated under reduced pressure
6. dissolutionThe resulting residue was dissolved in 1,4-dioxane (6 mL)
7. stirringthe mixture was stirred at 100° C. under a nitrogen atmosphere for 16 hours
8. customthe solvent was evaporated under reduced pressure
9. stirringthe mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour
10. customto separate the layers
11. customThe resulting organic layer was separated
12. washwashed with saturated sodium chloride solution
13. dry with materialdried with anhydrous sodium sulfate
14. customthe solvent was evaporated under reduced pressure
15. customThe residue was purified by silica gel column chromatography (hexane

ORD record

ord-94e0ba7de3e140d1a2bf01148ff5f58a

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08476253B2