Hydrochloric Acid → 3-{3-[(2-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}ethyl)amino]phenyl}isonicotinic Acid

HRID 31396Notes

Reaction equation

CC1[N:3]([C:7]2[CH:8]=[C:9]([C:13]3[CH:22]=[N:21][CH:20]=[CH:19][C:14]=3[C:15]([O:17]C)=[O:16])[CH:10]=[CH:11][CH:12]=2)[CH2:4][CH2:5][N:6]=1.[Cl:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C@H:27]1[O:29][CH2:28]1.[OH-].[Na+].Cl>C1(C)C=CC=CC=1.CO>[Cl:23][C:24]1[CH:25]=[C:26]([C@@H:27]([OH:29])[CH2:28][NH:6][CH2:5][CH2:4][NH:3][C:7]2[CH:8]=[C:9]([C:13]3[CH:22]=[N:21][CH:20]=[CH:19][C:14]=3[C:15]([OH:17])=[O:16])[CH:10]=[CH:11][CH:12]=2)[CH:30]=[CH:31][CH:32]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A solution of methyl 3-[3-(2-methyl-4,5-dihydro-1H-imidazol-1-yl)phenyl]isonicotinate (0.25 g) and (R)-3-chlorostyrene oxide (0.13 g) in anhydrous toluene (2 ml) was heated at reflux (ca. 110° C.) for 18 h. The mixture was cooled to ca. 50° C., 1M sodium hydroxide solution (4.8 ml) and methanol (3 ml) were added over 5-10 min. The apparatus was configured to distill out 4 ml of solvents under atmospheric pressure. The homogeneous mixture obtained was heated at reflux for 2 h. The mixture was cooled to <50° C., and concentrated hydrochloric acid (36%, 0.3 ml) was added dropwise to adjust pH to 7. The aqueous solution was loaded on to silica gel column and eluted with a mixture of dichloromethane and methanol (8/2, v/v). The product was isolated as 0.2 g (57%) of hygroscopic brown solid.

Workup

temperatureThe mixture was cooled to ca. 50° C.
distillationto distill out 4 ml of solvents under atmospheric pressure
customThe homogeneous mixture obtained
temperaturewas heated
temperatureat reflux for 2 h
temperatureThe mixture was cooled to <50° C.
washeluted with a mixture of dichloromethane and methanol (8/2

Sources & evidence

ORD record: ord-24b5a4e756844a359bc5833cf52e25b3
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07425639B2

Reaction notes

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