(R)-(-)-2-Amino-1-propanol → (R)-ethyl 1-(1-hydroxypropan-2-yl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 2061861Notes

Reaction equation

CN(C)/[CH:3]=[C:4](/[C:10](=[O:19])[C:11]1[CH:16]=[C:15]([I:17])[CH:14]=[CH:13][C:12]=1F)\[C:5]([O:7][CH2:8][CH3:9])=[O:6].[NH2:21][C@H:22]([CH3:25])[CH2:23][OH:24]>C1COCC1>[OH:24][CH2:23][C@H:22]([N:21]1[C:12]2[C:11](=[CH:16][C:15]([I:17])=[CH:14][CH:13]=2)[C:10](=[O:19])[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:3]1)[CH3:25]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of ethyl 3-(dimethylamino)-2-(2-fluoro-5-iodobenzoyl)acrylate (Intermediate 24, 1 g, 2.56 mmol) dissolved in THF (10 mL) was added (R)-2-aminopropan -1-ol (300 mg, 2.56 mmol). The reaction mixture was stirred at 60° C. for 2 h. The reaction mixture was concentrated under reduced pressure, and the resulting residue was suspended in DMF (10 mL). Potassium carbonate was added (1.06 g, 7.67 mmol, 3 equiv.), and the reaction mixture was stirred at 70° C. for 18 h. The reaction mixture was cooled down to room temperature and quenched with 1 N HCl. The precipitate that formed was collected by filtration, washed with water and hexanes to provide (R)-ethyl 1-(1-hydroxypropan-2-yl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate (446 mg, 39%).

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
additionPotassium carbonate was added (1.06 g, 7.67 mmol, 3 equiv.)
stirringthe reaction mixture was stirred at 70° C. for 18 h
temperatureThe reaction mixture was cooled down to room temperature
customquenched with 1 N HCl
customThe precipitate that formed
filtrationwas collected by filtration
washwashed with water and hexanes

Sources & evidence

ORD record: ord-501bc739298d4c70a83e5f7c4c30538a
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08283361B2

Reaction notes

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