Methanol → Tert-butyl 2-(3-methoxyquinolin-6-yl)acetate

HRID 2176594Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:7][CH:6]=2.CO.[CH2:22](P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1C=CC=CC=1>[CH3:22][O:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:7][CH:6]=2

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate (0.1 g, 0.4 mmol) in benzene (5 mL) was added methanol (0.05 ml, 1 mmol) and tributylphosphine (0.1 ml, 0.6 mmol). The resulting mixture was cooled to 0° C. followed by adding 1,1′-(azodicarbonyl)dipiperidine (0.1 g, 0.6 mmol). After 10 min, ice bath was removed; the reaction mixture was warmed up to rt. The reaction mixture was continued to stir for 20 h. TLC showed about 80% conversion. More MeOH (1 ml), tributylphosphine (0.05 mL), and ADDP (50 mg) were added and allowed to stir for 3 h. Hexane was added to the reaction mixture and dihydro-ADDP separated out and was filtered off. The filtrate was concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep®, P/N 68-2203-027, 40 g SiO2) to afford the desired product as colorless liquid. MS m/z: 274.3 (M+H). Calc'd. for C16H19NO3—273.2

Workup

customice bath was removed
temperaturethe reaction mixture was warmed up to rt
additionMore MeOH (1 ml), tributylphosphine (0.05 mL), and ADDP (50 mg) were added
stirringto stir for 3 h
additionHexane was added to the reaction mixture and dihydro-ADDP
customseparated out
filtrationwas filtered off
concentrationThe filtrate was concentrated
customThe crude product was purified

Sources & evidence

ORD record: ord-b922f9cd94784abebd8531158135e597
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09066954B2

Reaction notes

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