Triethylamine → HCID 11335793, compound

Temperature

0 °C

A solution of (±)-trans-2-[4-(4-chlorobenzyl)piperidin-1-yl]-cyclohexanol (390 mg, 1.27 mmol) in CH2Cl2 (6 mL) at 0° C. was treated successively with Et3N (350 μL, 2.53 mmol) and MeSO2Cl (194 μL, 2.53 mmol), stirred at 0° C. for 2 hours, and partitioned between CH2Cl2 and 10% NH4OH. The aqueous phase was extracted with CH2Cl2 and the extracts were washed with brine, dried and concentrated. A solution of the residue in THF (3 mL) and 28–30 wt % NH4OH (1.2 mL) was stirred at 70° C. for 24 hours, allowed to cool to room temperature, and partitioned between EtOAc and 1 N NaOH. The aqueous phase was extracted with EtOAc and the extracts were washed with brine, dried and concentrated. Chromatography of the residue on alumina with 1:3 EtOAc:MeOH to 100% MeOH and a subsequent chromatography on alumina with 20:1 hexanes:EtOAc to 100% EtOAc followed by 3:1 EtOAc:MeOH to 100% MeOH gave the product (260 mg, 67%) as a tan oil which solidified upon standing: mp 69.1–70.4° C.; 1H NMR δ 1.03–1.34 (m, 6H), 1.37–1.52 (m, 1H), 1.57–1.77 (m, 5H), 1.92–2.05 (m, 3H), 2.48 (d, J=7.0 Hz, 2H), 2.45–2.64 (m, 3), 2.73 (m, 1H), 7.06 (m, 2H), 7.23 (m, 2H); MS m/z 307 (M+H)+.

1. custompartitioned between CH2Cl2 and 10% NH4OH
2. extractionThe aqueous phase was extracted with CH2Cl2
3. washthe extracts were washed with brine
4. customdried
5. concentrationconcentrated
6. stirringA solution of the residue in THF (3 mL) and 28–30 wt % NH4OH (1.2 mL) was stirred at 70° C. for 24 hours
7. temperatureto cool to room temperature
8. custompartitioned between EtOAc and 1 N NaOH
9. extractionThe aqueous phase was extracted with EtOAc
10. washthe extracts were washed with brine
11. customdried
12. concentrationconcentrated

ORD record

ord-0f4337f0250744caba09a9cd7d0f2653

Source dataset

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07019007B2