Hydrochloric Acid → 8-Methyl-2-piperazin-1-ylmethyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

HRID 860011Notes

Reaction equation

C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C@@H:15]2[O:29][C:19]3=[C:20]4[C:25](=[CH:26][CH:27]=[C:18]3[O:17][CH2:16]2)[N:24]=[C:23]([CH3:28])[CH:22]=[CH:21]4)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.[OH-].[Na+]>C(OCC)(=O)C.C(OCC)C.CO>[CH3:28][C:23]1[CH:22]=[CH:21][C:20]2[C:25](=[CH:26][CH:27]=[C:18]3[O:17][CH2:16][CH:15]([CH2:14][N:11]4[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]4)[O:29][C:19]3=2)[N:24]=1

Participants

Conditions

Temperature: 35 °C

Procedure

To an ice-cold solution of (2S)-4-(8-methyl-2,3-dihydro-[1,4]dioxino[2,3-f]quinolin-2-ylmethyl)-piperazine 1 carboxylic acid tert-butyl ester of Step A′ (0.550 g, 1.37 mmol) in ethyl acetate (8 mL) is added dropwise 1 M hydrochloric acid in diethyl ether (15 mL). The mixture is allowed to come to room temperature, diluted with methanol (10–15 mL) and warmed at 35° C. until the reaction is complete by TLC. The solvents are removed in vacuo and the residue is slurried in diethyl ether. The solid is collected and dried in vacuo. The free base is prepared by basifying an aqueous solution of the hydrochloride salt with concentrated aqueous sodium hydroxide, followed by extraction with dichloromethane. The title compound is obtained as a thick oil (quantitative yield).

Workup

customto come to room temperature
customThe solvents are removed in vacuo
customThe solid is collected
customdried in vacuo
customThe free base is prepared
extractionfollowed by extraction with dichloromethane

Sources & evidence

ORD record: ord-b3629f9b55684d2daac472d056dec158
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07153849B2

Reaction notes

Loading…