Hydrochloric Acid → HCID 68983099, compound

HRID 347897Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([F:18])[CH:17]=1)[O:5][C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12](=[O:14])[CH3:13])[CH2:7]1.C(OCC)(=O)C.[ClH:25]>CCOCC>[ClH:25].[NH2:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([F:18])[CH:17]=1)[O:5][C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12](=[O:14])[CH3:13])[CH2:7]1

Participants

Conditions

Temperature: 0 °C

Procedure

A 22 L 3-neck RBF equipped with a cooling bath, an addition funnel, mechanical stirrer, thermocouple and nitrogen bubbler was purged with nitrogen for at least ten minutes. The flask was charged with 0.612 kg (2.43 mol) 1-[(R)-3-(3-amino-5-fluoro-phenoxy) -piperidin-1-yl]-ethanone and 12.2 L (20 vol) ethyl acetate. The solution was cooled to 0±5° C. in an ice/brine bath, and 1.46 L (2.92 mol) 2M HCl in ether was added dropwise for 20 minutes, maintaining the internal temperature below 10° C. The solution stirred for 2 hours at 0±5° C., and the solid was filtered under a nitrogen atmosphere and rinsed with 6.0 L (10 vol) ethyl acetate. The solid was dried at 50±5° C. under vacuum for 2 days to afford 693 g of 1-[(R)-3-(3-amino-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone HCl salt in 99% yield as an off-white solid (theoretical yield=0.700 kg, purity=94.2% and 97.6% ee).

Workup

customA 22 L 3-neck RBF equipped with a cooling bath, an addition funnel, mechanical stirrer
customthermocouple and nitrogen bubbler was purged with nitrogen for at least ten minutes
temperaturemaintaining the internal temperature below 10° C
filtrationthe solid was filtered under a nitrogen atmosphere
washrinsed with 6.0 L (10 vol) ethyl acetate
customThe solid was dried at 50±5° C. under vacuum for 2 days

Sources & evidence

ORD record: ord-2c7e1339e76a48a1a6afa507874e84cc
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07176222B2

Reaction notes

Loading…