Cesium carbonate → (R)-2-chloro-4-(1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyridine

HRID 1499215Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([N+]([O-])=O)[CH:5]=[CH:4][N:3]=1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([C@@H:18]([OH:23])[C:19]([F:22])([F:21])[F:20])=[C:14]([N:24]2[CH:28]=[CH:27][C:26]([CH3:29])=[N:25]2)[CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[Cl:1][C:2]1[CH:7]=[C:6]([O:23][C@H:18]([C:15]2[CH:16]=[CH:17][C:12]([Cl:11])=[CH:13][C:14]=2[N:24]2[CH:28]=[CH:27][C:26]([CH3:29])=[N:25]2)[C:19]([F:22])([F:21])[F:20])[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 2-chloro-4-nitropyridine (200 mg, 1.00 mmol) in 1,4-dioxane (6 mL) was added. (R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethanol (368 mg, 1.27 mmol), and Cs2CO3 (828 mg, 2.54 mmol). The reaction was heated to 80° C. for 12 h, then cooled to RT, diluted with water, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase silica gel column (EtOAc/heptane) provided (R)-2-chloro-4-(1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyridine as an off-white solid.

Workup

temperaturecooled to RT
extractionextracted with EtOAc
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by normal phase silica gel column (EtOAc/heptane)

Sources & evidence

ORD record: ord-972ef6ea135b4d459c0c56843d2a179f
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199994B2

Reaction notes

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