4-Chlorobenzaldehyde → 1-(4-Chlorophenyl)-2-[3-(2,6-difluorophenyl)-[1,2,4]triazin-6-yl]-ethanol

HRID 2085926Notes

Reaction equation

C([Li])CCC.C(NC(C)C)(C)C.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=1[C:21]1[N:22]=[N:23][C:24]([CH3:27])=[CH:25][N:26]=1.[Cl:28][C:29]1[CH:36]=[CH:35][C:32]([CH:33]=[O:34])=[CH:31][CH:30]=1>O1CCCC1>[Cl:28][C:29]1[CH:36]=[CH:35][C:32]([CH:33]([OH:34])[CH2:27][C:24]2[N:23]=[N:22][C:21]([C:15]3[C:14]([F:13])=[CH:19][CH:18]=[CH:17][C:16]=3[F:20])=[N:26][CH:25]=2)=[CH:31][CH:30]=1

Participants

Conditions

Temperature: -50 °C

Procedure

At −20° C., 1.5 ml of n-butyllithium (1.6M in hexane) are added to 202 mg of diisopropylamine in 6 ml of tetrahydrofuran. After 15 min. the reaction mixture is cooled to −50° C. and 0.414 g of 3-(2,6-difluorophenyl)-6-methyl-[1,2,4]triazine in 2 ml of tetrahydrofuran is added dropwise. After 20 min. the mixture is cooled to −70° C., 0.281 g of 4-chlorobenzaldehyde in 3 ml of tetrahydrofuran is added dropwise and the mixture is then stirred at −70° C. for 2 h. The reaction mixture is then poured into ice-water and extracted with ethyl acetate; the organic phase is concentrated and the residue is purified by means of flash chromatography. In this way 1-(4-chlorophenyl)-2-[3-(2,6-difluorophenyl)-[1,2,4]triazin-6-yl]-ethanol is obtained in the form of a light-brown resin. After recrystallisation from diethyl ether/hexane, 1-(4-chlorophenyl)-2-[3-(2,6-difluorophenyl)-[1,2,4]triazin-6-yl]-ethanol is obtained in the form of beige crystals having a melting point of 98-102° C.

Workup

temperatureAfter 20 min. the mixture is cooled to −70° C.
extractionextracted with ethyl acetate
concentrationthe organic phase is concentrated
customthe residue is purified by means of flash chromatography

Sources & evidence

ORD record: ord-0993a295f8c942f9a02da91b052d63f6
Source dataset: uspto-grants-2004_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06723720B2

Reaction notes

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