tert-Butanol → Tert-butyl 5-(6-bromo-2-phenylquinolin-3-yl)pentanoate

HRID 927023Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([CH2:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:5]2.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.[CH3:38][C:39](O)([CH3:41])[CH3:40]>C(Cl)Cl.C(=O)(O)[O-].[Na+]>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([CH2:18][CH2:19][CH2:20][CH2:21][C:22]([O:24][C:39]([CH3:41])([CH3:40])[CH3:38])=[O:23])=[CH:5]2

Participants

Conditions

Temperature: 0 °C

Procedure

5-(6-Bromo-2-phenylquinolin-3-yl)pentanoic acid (1A, 4.00 g, 10.4 mmol) was dissolved in DCM (100 mL). The flask was cooled to 0° C. in an ice/water bath before TFAA (14.7 mL, 104 mmol) was slowly added. After stirring at 0° C. for 1 h, tBuOH (29.9 mL) was gradually added and the reaction mixture was allowed to warm to RT overnight. The mixture was diluted with DCM and sat. Sodium bicarbonate. The biphasic solution was separated and the aqueous layer was extracted with DCM (3×). The combined organic phase was dried over anhydrous sodium sulfate and concentrated. Chromatography (5-100% EtOAc/hexanes) afforded tert-butyl 5-(6-bromo-2-phenylquinolin-3-yl)pentanoate (18, 3.71 g; Yield=81%, LCMS (M+H)=440).

Workup

additionwas slowly added
temperatureto warm to RT overnight
customThe biphasic solution was separated
extractionthe aqueous layer was extracted with DCM (3×)
dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
concentrationconcentrated

Sources & evidence

ORD record: ord-d6f7f2207a4141aab2f11e560b6dadb0
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290453B2

Reaction notes

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