Diisopropylamine → (2,3,4-Trimethoxy-6-methylphenyl)(2,3,6-trichloro-5-trifluoromethyl-4-pyridyl)methanol

HRID 1912269Notes

Reaction equation

C([Li])CCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[C:19]([Cl:20])=[CH:18][C:17]([C:21]([F:24])([F:23])[F:22])=[C:16]([Cl:25])[N:15]=1.ClC1C(Cl)=C([Li])C(C(F)(F)F)=C(Cl)N=1.[CH3:40][O:41][C:42]1[C:49]([O:50][CH3:51])=[C:48]([O:52][CH3:53])[CH:47]=[C:46]([CH3:54])[C:43]=1[CH:44]=[O:45]>C(OCC)C.C1(C)C=CC=CC=1.O>[CH3:40][O:41][C:42]1[C:49]([O:50][CH3:51])=[C:48]([O:52][CH3:53])[CH:47]=[C:46]([CH3:54])[C:43]=1[CH:44]([C:18]1[C:17]([C:21]([F:24])([F:22])[F:23])=[C:16]([Cl:25])[N:15]=[C:14]([Cl:13])[C:19]=1[Cl:20])[OH:45]

Participants

Conditions

Temperature: -78 °C

Procedure

17 ml (25 mmol) of n-butyllithium (1.5 mol/l hexane solution) was dropwise added at 0° C. to a solution having 3.6 ml (25 mmol) of diisopropylamine dissolved in 60 ml of diethyl ether, followed by stirring for 45 minutes. The solution was cooled to −78° C., and a solution having 6.0 g (24 mmol) of 2,3,6-trichloro-5-trifluoromethylpyridine dissolved in 8 ml of diethyl ether was added, followed by stirring for 25 minutes to prepare 2,3,6-trichloro-5-trifluoromethyl-4-pyridyllithium, and then a solution having 5.0 g (24 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 12 ml of toluene was added, followed by stirring for 1 hour. 30 ml of water was added to the mixture to terminate the reaction, and the aqueous layer was extracted with ethyl acetate. Then, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure to obtain (2,3,4-trimethoxy-6-methylphenyl)(2,3,6-trichloro-5-trifluoromethyl-4-pyridyl)methanol (melting point 131 to 135° C.). (b) 2.7 ml (19 mmol) of triethylamine and 0.9 g of 5% palladium carbon were added to a solution having 2,3,4-trimethoxy-6-methylphenyl)(2,3,6-trichloro-5-trifluoromethyl-4-pyridyl)methanol obtained in Step (a) dissolved in 200 ml of methanol, followed by stirring under a hydrogen atmosphere for 14 hours. The mixture was subjected to filtration, 30 ml of water was added, and methanol was distilled off under reduced pressure. After extraction with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 2.38 g (yield: 24%) of (2,3,4-trimethoxy-6-methylphenyl)(2,5-dichloro-3-trifluoromethyl-4-pyridyl)methanol (melting point 162 to 165° C.). (c) 14 g of manganese dioxide was added to a solution having 3.5 g (8.2 mmol) of (2,3,4-trimethoxy-6-methylphenyl)(2,5-dichloro-3-trifluoromethyl-4-pyridyl)methanol obtained in Step (b) dissolved in 100 ml of toluene, followed by stirring under reflux with heating for 6 hours. The mixture was cooled and then subjected to filtration, and toluene was distilled off under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 3.1 g (yield: 89%) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,5-dichloro-3-trifluoromethylpyridine (melting point 106 to 109° C.).

Workup

additionwas added
stirringby stirring for 25 minutes
additionwas added
stirringby stirring for 1 hour
customto terminate
customthe reaction
extractionthe aqueous layer was extracted with ethyl acetate
dry with materialThen, the organic layer was dried over anhydrous sodium sulfate
filtrationsubjected to filtration
distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record: ord-52c2a1e16dd34d0d8ccfed2045986d54
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609150B2

Reaction notes

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