Hydrochloric Acid → HCID 20098198, compound

HRID 487856Notes

Reaction equation

Br[C:2]1[CH:6]=[CH:5][S:4][CH:3]=1.[Li]CCCC.CCCCCC.[F:18][CH:19]([F:40])[C:20]1[C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:23]([CH:34]=[O:35])=[C:22]([C:36]([F:39])([F:38])[F:37])[N:21]=1.Cl>C1COCC1.O>[F:40][CH:19]([F:18])[C:20]1[C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:23]([CH:34]([OH:35])[C:2]2[CH:6]=[CH:5][S:4][CH:3]=2)=[C:22]([C:36]([F:39])([F:37])[F:38])[N:21]=1

Participants

Conditions

Temperature: -70 °C

Procedure

To a solution of 3-bromothiophene (4 g 24.5 mmol) in dry THF (80 mL) cooled to -70° C. was added dropwise 2.5M n-BuLi in hexane (11 mL, 27.5 mmol). The mixture was stirred for one-half h. A solution of methyl 2-(difluoromethyl)-5-formyl-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (6.6 g, 19.5 mmol) in anhydrous THF (20 mL) was added dropwise and stirring was continued for 1 h while the temperature was maintained at -70° C. The mixture was allowed to warm to RT and then poured into iced water, acidified with conc. HCl and extracted with methylene chloride. The extract was washed with water and brine, dried (MgSO4), and conc. The residue was purified by chromatography with 10% ethyl acetate/cyclohexane to yield 5.6 g of methyl 2-(difluoromethyl)-5-(hydroxy-3-thienylmethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate, a 68.9% yield.

Workup

stirringstirring
temperatureto warm to RT
extractionextracted with methylene chloride
washThe extract was washed with water and brine
dry with materialdried (MgSO4)
customconc. The residue was purified by chromatography with 10% ethyl acetate/cyclohexane

Sources & evidence

ORD record: ord-cc71ec14a66f4742b7ca9541edec4a20
Source dataset: uspto-grants-1994_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05298479

Reaction notes

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