3-Bromo-1,1,1-trifluoro-2-propanone → 2-[4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazol-2-yl]pyridine

HRID 1166356

Reaction equation

[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[NH:13])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(=O)(O)[O-].[Na+].Br[CH2:26][C:27](=[O:32])[C:28]([F:31])([F:30])[F:29]>C(O)(C)C>[OH:32][C:27]1([C:28]([F:31])([F:30])[F:29])[CH2:26][N:11]([C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][CH:9]=2)[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[N:13]1

Participants

Conditions

Temperature: 77.5 °C

Procedure

To a mixture of the amidine of step 1 (4.4 g, 16 mmol) and sodium bicarbonate (2.7 g, 32 mmol) in isopropanol (400 ml), 3-bromo-1,1,1-trifluoroacetone (2.5 ml, 24 mmol) was added. After heating at 75-80° C. for 24 hours, the reaction mixture was cooled and filtered. The residue was washed with methylene chloride and the combined organic fractions were dried over sodium sulfate, filtered and concentrated. The crude product (16.2 g) was purified by chromatography (silica gel, ethyl acetate/toluene 1/1) to give 2-[4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazol-2-yl]pyridine (1.1 g, 18%) as a white solid: mp 195-198° C. Anal. Calc'd. for C16H14N3SO3F3: C, 49.87, H, 3.66, N, 10.90. Found: C, 50.13, H, 3.66, N, 10.30.

Workup

additionwas added
temperaturethe reaction mixture was cooled
filtrationfiltered
washThe residue was washed with methylene chloride
dry with materialthe combined organic fractions were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude product (16.2 g) was purified by chromatography (silica gel, ethyl acetate/toluene 1/1)

Sources & evidence

ORD record: ord-c8412f9c37364d1bb9972e301cd154c8
Source dataset: uspto-grants-2003_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06613789B2

Linked notes

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