1,4-Dioxane → Tert-butyl-3-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline-6-carbonyl)azetidine-1-carboxylate

HRID 526851Notes

Reaction equation

[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([OH:24])[CH:13]3[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]3)[CH:10]=2)[N:5]=[C:4]([O:25][CH3:26])[C:3]=1[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=1.O1CCOCC1>O=[Mn]=O.C1COCC1>[C:20]([O:19][C:17]([N:15]1[CH2:14][CH:13]([C:12]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]=[C:4]([O:25][CH3:26])[C:3]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)=[C:2]3[Cl:1])=[O:24])[CH2:16]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]

Participants

Conditions

Temperature: 85 °C

Procedure

To a flask containing tert-butyl 3-((4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(hydroxy)methyl)azetidine-1-carboxylate (4.75 g, 8.85 mmol, Intermediate 13: step a) was added 1,4-dioxane (200 mL) and THF (100 mL) to give a homogeneous solution. Activated MnO2 (5.0 g, 57.5 mmol) was then introduced and the mixture was heated to 85° C. After 3 hours the reaction mixture was filtered through Celite® while still warm and rinsed with additional THF and concentrated. Chromatography on silica gel (10% acetone-hexane increasing to 25% acetone) provided the title compound as an off white solid.

Workup

customto give a homogeneous solution
filtrationAfter 3 hours the reaction mixture was filtered through Celite®
temperaturewhile still warm
washrinsed with additional THF
concentrationconcentrated

Sources & evidence

ORD record: ord-559cddd3330e4ceaae214eee36fb43c7
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346782B2

Reaction notes

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