Hydrochloric Acid → 2-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole-6-carboxylic acid

HRID 1776859Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:17]([C:19]([O:21]CC)=[O:20])[N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=4[CH:15]=[C:7]3[C:6]=2[N:24]=1.[Li+].[OH-].Cl>O1CCOCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:17]([C:19]([OH:21])=[O:20])[N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=4[CH:15]=[C:7]3[C:6]=2[N:24]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of ethyl 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-6-carboxylate (606 mg, 1.75 mmol) and LiOH (168 mg, 7.00 mmol) in dioxane/H2O (6 mL/5 mL) was stirred at 80° C. for 2 hours. The reaction was monitored using TLC. When the reaction was completed, 1 N HCl aqueous was added to the mixture until pH 4. The mixture was extracted with EtOAc (10 mL*3). The combined organic layer was washed with brine (30 mL), dried over Na2SO4 and concentrated under reduce pressure, afforded 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-6-carboxylic acid (590 mg, yield: 99%). 1H-NMR (400 MHz, DMSO-d6) δ 7.74 (d, J=8.8 Hz, 1H), 7.43˜7.56 (m, 2H), 7.37 (s, 1H), 7.25˜7.34 (m, 1H), 7.15 (s, 1H), 6.92˜7.02 (m, 1H). MS (M+H)+: 319.

Workup

extractionThe mixture was extracted with EtOAc (10 mL*3)
washThe combined organic layer was washed with brine (30 mL)
dry with materialdried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-cfd37d9f427d458f8fce0c8c1a8f259e
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09265773B2

Reaction notes

Loading…