Pinacol → 5-Chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)pyridine

HRID 539918Notes

Reaction equation

HRID 539918 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([F:10])=[C:6]([CH:9]=1)[CH:7]=[O:8].[CH3:11][C:12](O)([C:14]([CH3:17])([OH:16])[CH3:15])[CH3:13].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:9]=[C:6]([CH:7]2[O:16][C:14]([CH3:17])([CH3:15])[C:12]([CH3:13])([CH3:11])[O:8]2)[C:5]([F:10])=[N:4][CH:3]=1

Participants

6

Reactant 3

HCID 6425PinacolHCID 521998p-Toluenesulfonic acid monohydrateHCID 404270055-Chloro-2-fluoropyridine-3-carbaldehyde

Product 1

HCID 679755975-Chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)pyridine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A flask fitted with a Dean-Stark trap was charged with a solution of 5-chloro-2-fluoronicotinaldehyde, 27, (8.95 g, 56.10 mmol) and 2,3-dimethylbutane-2,3-diol (8.00 g, 67.70 mmol) and p-toluene sulfonic acid mono hydrate (0.54 g, 2.81 mmol) in toluene (250 mL) and heated to vigorous reflux for 3 hr. The mixture was cooled, diluted with EtOAc, washed with NaHCO3 (2×) and brine (1×). The organic phase was dried over Na2SO4, filtered through a silica plug and concentrated in vacuo. A crystalline solid formed on standing (14.47 g): 1H NMR (300.0 MHz, CDCl3) δ 8.12 (s, 1H), 7.97 (dd, J=2.7, 7.8 Hz, 1H), 6.08 (s, 1H), 1.33 (s, 3H) and 1.26 (s, 3H) ppm.

Workup

  1. customA flask fitted with a Dean-Stark trap
  2. temperatureheated
  3. temperatureto vigorous reflux for 3 hr
  4. temperatureThe mixture was cooled
  5. washwashed with NaHCO3 (2×) and brine (1×)
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered through a silica plug
  8. concentrationconcentrated in vacuo
  9. customA crystalline solid formed

Sources & evidence

ORD record
ord-d15069a9bdfa4ab38f82c5604e418a62
Source dataset
uspto-grants-2014_10
Patent number
US08871774B2

Reaction notes

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