Hydrochloric Acid → 4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-{6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl}ethyl}pyridine

HRID 567947Notes

Reaction equation

C([CH:6]([C:40]1[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=1)[CH:7]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH:33]([F:35])[F:34])=[C:28]([O:36][CH:37]([F:39])[F:38])[CH:27]=1)[C:8]1[CH:9]=[N:10][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)=[CH:12][CH:13]=1)(OCC)=O.C1COCC1.[Li+].[OH-].Cl>O.CO>[F:39][CH:37]([F:38])[O:36][C:28]1[CH:27]=[C:26]([CH:7]([C:8]2[CH:9]=[N:10][C:11]([O:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)=[CH:12][CH:13]=2)[CH2:6][C:40]2[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=2)[CH:31]=[CH:30][C:29]=1[O:32][CH:33]([F:35])[F:34]

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of the crude ester from Step 4 above in 25 mL of a 3:1:1 mixture of THF:MeOH:water, was added 5.1 mL (10.3 mmol) of a 2 N solution of LiOH. The resulting solution was stirred at 65° C. for 1.5 h, cooled down to room temperature followed by the addition of 10 mL of a 1.0 N HCl solution. The resulting mixture was rotovaped down to evaporate MeOH and the aqueous residue was diluted with ethyl acetate. The organic layer was washed with water and brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (50% Ethyl acetate/hexane) to afford the desired pyridine as an oil (380 mg, 68% from Step 2).

Workup

temperaturecooled down to room temperature
customto evaporate MeOH
additionthe aqueous residue was diluted with ethyl acetate
washThe organic layer was washed with water and brine
dry with materialdried over MgSO4
concentrationconcentrated under reduced pressure
customThe residue was purified by flash chromatography on silica gel (50% Ethyl acetate/hexane)
customto afford the desired pyridine as an oil (380 mg, 68% from Step 2)

Sources & evidence

ORD record: ord-a2fbb9c7d1604bdea08a9453bafcd429
Source dataset: uspto-grants-2001_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06180650B2

Reaction notes

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