Hydrochloric Acid → Hydrochloric Acid

HRID 870907Notes

Reaction equation

C(OC(=O)[NH:7][C@@H:8]([CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]2[C:24]3[C:19](=[CH:20][N:21]=[CH:22][CH:23]=3)[CH:18]([CH:25]3[CH2:27][CH2:26]3)[O:17][C:15]=2[CH:16]=1)(C)(C)C.[ClH:33].O1CCOCC1>C(Cl)Cl>[CH:25]1([CH:18]2[C:19]3=[CH:20][N:21]=[CH:22][CH:23]=[C:24]3[C:14]3[CH:13]=[CH:12][C:11]([O:10][CH2:9][C@@H:8]([NH2:7])[CH2:28][CH:29]([CH3:30])[CH3:31])=[CH:16][C:15]=3[O:17]2)[CH2:27][CH2:26]1.[ClH:33]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of tert-butyl((2S)-1-((5-cyclopropyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (250 mg, 0.570 mmol) in CH2Cl2 (4 mL) cooled to 0° C. was added 1N HCl in dioxane (2 mL, 0.570 mmol) slowly over a period of 5 min. The reaction mixture was stirred at 0° C. for 5 min then was warmed to room temperature and allowed to stir for 2 h. The solvents were removed by concentration under reduced pressure. The crude product was washed with ethyl acetate to yield (2S)-1-(5-cyclopropyl-5H-chromeno[3,4-c]pyridin-8-yloxy)-4-methylpentan-2-amine as an HCl salt (240 mg, 42% yield). LCMS (ESI) m/e 339.2 [(M+H)+, calcd for C21H27N2O2 339.2]; LC/MS retention time (Method C): tR=1.28 min. The diastereomeric mixture of amines was resolved by chiral preparative HPLC (0.2% DEA in n-hexane, ethanol).

Workup

temperaturethen was warmed to room temperature
stirringto stir for 2 h
customThe solvents were removed by concentration under reduced pressure
washThe crude product was washed with ethyl acetate

Sources & evidence

ORD record: ord-10364fb653604cbf8623d26a5560ab03
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969564B2

Reaction notes

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