Water → ((1R,3R)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methyl dihydrogen phosphate

Participants

Reaction Steps

To a stirred solution of ((1R,3R)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (Example 1, 10 mg, 0.030 mmol) in anhydrous acetonitrile (1 mL) at 0° C. was added pyrophosphoryl chloride (0.042 mL, 0.303 mmol). The clear solution obtained was stirred at the same temperature for 5 min and at RT overnight. After water (0.4 mL) was added, the mixture was stirred at RT for 1 h. Purification using reverse phase HPLC (Luna Axia 5μ c18 30×100 mm, 10 min. gradient from 40% to 100% of Solvent B, Solvent A: 0.1% TFA in water, Solvent B: 0.1% TFA in MeCN), concentration and lyophilization gave ((1R,3R)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methyl dihydrogen phosphate (2 mg, 4.15 μmol, 13.68% yield) as a white solid. HPLC retention time=3.94 min (Condition C); LC/MS M+1=410; 1H NMR (500 MHz, methanol-d4+KOH) δ 6.97-6.87 (m, 3H), 3.77-3.71 (m, 1H), 3.71-3.66 (m, 1H), 2.83-2.70 (m, 3H), 2.32 (dd, J=16.2, 10.7 Hz, 1H), 2.14-1.98 (m, 2H), 1.96-1.83 (m, 2H), 1.74-1.60 (m, 3H), 1.59-1.49 (m, 1H), 1.45-1.26 (m, 11H), 0.94-0.87 (m, 3H), one proton under methanol solvent peak (˜3.3 ppm).

Provenance & Evidence