Water → 1-(4-(4-Chloro-2-fluorophenyl)pyridin-3-yl)-2,2,2-trifluoroethanol

HRID 870950Notes

Reaction equation

HRID 870950 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH:14]=[O:15])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:16])[CH:3]=1.[Si]([C:21]([F:24])([F:23])[F:22])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].O>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][N:11]=[CH:12][C:13]=2[CH:14]([OH:15])[C:21]([F:24])([F:23])[F:22])=[C:4]([F:16])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 866958904-(4-Chloro-2-fluorophenyl)nicotinaldehyde

Product 1

HCID 897912891-(4-(4-Chloro-2-fluorophenyl)pyridin-3-yl)-2,2,2-trifluoroethanolYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred solution of 4-(4-chloro-2-fluorophenyl)nicotinaldehyde (1.8 g, 7.64 mmol) (prepared as described in Example 5, Part B) and TMS-CF3 (0.521 mL, 3.52 mmol) in dichloromethane (20 mL) was stirred at 0° C. for 20 min. TBAF (1.0 M in THF) (0.4 mL, 1.528 mmol) was added dropwise slowly and the solution stirred for 90 min. Water was added and the solution extracted with dichloromethane (2×25 mL). The combined organic layers were washed with brine, dried over sodium sulphate, concentrated and purified by Prep. TLC using 25% ethyl acetate in hexane to give 1-(4-(4-chloro-2-fluorophenyl)pyridin-3-yl)-2,2,2-trifluoroethanol (1 g, 2.64 mmol, 35% yield) as a yellow oil. LCMS (ESI) m/e 306.0 [(M+H)+, calcd for C13H9ClF4NO 306.02]; LC/MS retention time (Method C): tR=2.05 min.

Workup

  1. extractionthe solution extracted with dichloromethane (2×25 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. custompurified by Prep

Sources & evidence

ORD record
ord-c01bdd8d80e24071ae231d455327c6eb
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

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