p-Toluenesulfonic acid monohydrate → HCID 67099573, compound

Temperature

50 °C

In a separate round-bottomed flask, 1-bromo-4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)benzene (487 mg, 1.3 μmol) and [Pd(PtBu3)Br]2 (105 mg, 135 μmol) were mixed. The reaction vessel was evacuated under vacuum and backfilled with argon. Toluene (5 mL) was added, and the mixture was heated to 50° C. for 5 minutes and then transferred by syringe to the enolate solution. The aryl bromide-Pd flask was rinsed with toluene (1 mL) and added to the reaction mixture. The resulting mixture was heated at 50° C. under nitrogen. After 90 minutes, the reaction was cooled to 23° C., diluted with EtOAc (100 mL), and washed with water (50 mL) and brine (50 mL). The organic layer was dried over MgSO4, concentrated in vacuo, and purified by silica gel chromatography (eluant: 4-6% EtOAc/hexane+1% TEA) affording the desired coupled product 1-tert-butyl ethyl 4-(4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)phenyl)piperidine-1,4-dicarboxylate. A solution of the 1-tert-butyl ethyl 4-(4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)phenyl)piperidine-1,4-dicarboxylate in EtOH (10 mL) and water (2 mL) was treated with p-toluenesulfonic acid monohydrate (69.3 mg, 364 μmol). The reaction was stirred at 23° C. for 30 minutes, and then diluted with EtOAc (100 mL) and washed with saturated NaHCO3 solution (2×50 mL) and brine (50 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluant: 12-16% EtOAc/hexane), affording 155 mg of 1-tert-butyl ethyl 4-(4-chloro-2-(3-ethoxy-3-oxoprop-1-ynyl)phenyl)piperidine-1,4-dicarboxylate. MS m/e=486.1 (M+Na)+.

1. customThe reaction vessel was evacuated under vacuum
2. additionToluene (5 mL) was added
3. customtransferred by syringe to the enolate solution
4. washThe aryl bromide-Pd flask was rinsed with toluene (1 mL)
5. additionadded to the reaction mixture
6. temperatureThe resulting mixture was heated at 50° C. under nitrogen
7. temperaturethe reaction was cooled to 23° C.
8. additiondiluted with EtOAc (100 mL)
9. washwashed with water (50 mL) and brine (50 mL)
10. dry with materialThe organic layer was dried over MgSO4
11. concentrationconcentrated in vacuo
12. custompurified by silica gel chromatography (eluant: 4-6% EtOAc/hexane+1% TEA)
13. customaffording the
14. washwashed with saturated NaHCO3 solution (2×50 mL) and brine (50 mL)
15. dry with materialdried over MgSO4
16. concentrationconcentrated in vacuo
17. custompurified by silica gel chromatography (eluant: 12-16% EtOAc/hexane)

ORD record

ord-489c091cbee240cdb734a42d8659722f

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07635715B2