Pyridine → (R)-3-((R)-(3-methoxypropoxy)(phenyl)methyl)piperidine-1-carbonyl chloride

(R)-tert-butyl 3-((R)-(3-methoxypropoxy)(phenyl)methyl)piperidine-1-carboxylate (219 mg, 0.603 mmol) was dissolved in 4M HCl in 1,4-dioxane (20 mL, 80 mmol) and stirred for 30 min. LC-MS showed removal of the Boc protecting group. The reaction mixture was concentrated and redissolved dry CH2Cl2 (5 mL). Pyridine (122 μL, 1.51 mmol, 2.5 equiv) was added. This solution was added dropwise under N2 to a solution of triphosgene (188 mg, 0.63 mmol, 1.05 equiv) in dry CH2Cl2 (5 mL) at −78° C. After 10 min, the reaction mixture was warmed to rt and stirred for 2 h. LC-MS showed the reaction was complete. 5% aq HCl (15 mL) was added and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2×30 ml). The combined organic layers were washed with satd aq NaHCO3 and brine, and dried over Na2SO4. Concentration afforded (R)-3-((R)-(3-methoxypropoxy)(phenyl)-methyl)piperidine-1-carbonyl chloride (188 mg, 96%) as a yellow oil. LC-MS (3 min) tR=1.83 min, m/z 344 (M+H2O). The crude product was used for the next step without further purification.

1. customremoval of the Boc protecting group
2. concentrationThe reaction mixture was concentrated
3. dissolutionredissolved dry CH2Cl2 (5 mL)
4. waitAfter 10 min
5. stirringstirred for 2 h
6. customthe layers were separated
7. extractionThe aqueous layer was extracted with CH2Cl2 (2×30 ml)
8. washThe combined organic layers were washed with satd aq NaHCO3 and brine
9. dry with materialdried over Na2SO4
10. concentrationConcentration

ORD record

ord-9df81902947a462fb3144f0aa4d294c9

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07754737B2