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

HRID 1499215
Notes
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Reaction equation

HRID 1499215 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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 7351522-Chloro-4-nitropyridineHCID 25210912(alphaR)-4-Chloro-2-(3-methyl-1H-pyrazol-1-yl)-alpha-(trifluoromethyl)benzenemethanol

Product 1

HCID 117942068(R)-2-chloro-4-(1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyridine

Reagents, catalysts & solvents 2

HCID 962
Water
Solvent
HCID 312751,4-DioxaneSolvent

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

  1. temperaturecooled to RT
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes