p-Toluenesulfonic acid monohydrate → (S)-2-Chloro-5-(2,2-dimethyl-1,3-dioxolan-4-yl)-3-fluoropyridine

HRID 920133Notes

Reaction equation

HRID 920133 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C@H:8]([OH:11])[CH2:9][OH:10])=[CH:4][C:3]=1[F:12].O.[C:14]1(C)[CH:19]=CC(S(O)(=O)=O)=C[CH:15]=1>COC(OC)(C)C>[Cl:1][C:2]1[C:3]([F:12])=[CH:4][C:5]([C@H:8]2[CH2:9][O:10][C:14]([CH3:19])([CH3:15])[O:11]2)=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 89310968(S)-1-(6-Chloro-5-fluoropyridin-3-yl)ethane-1,2-diol

Product 1

HCID 89311091(S)-2-Chloro-5-(2,2-dimethyl-1,3-dioxolan-4-yl)-3-fluoropyridineYield 864.9%

Reagents, catalysts & solvents 1

HCID 64952,2-DimethoxypropaneSolvent

Conditions

Temperature
25 °C

Procedure

A suspension of 113 (5.39 g, 28.2 mmol) in 2,2-dimethoxypropane (58 mL, Sigma-Aldrich) was cooled with an ice bath. Para-toluene sulfonic acid monohydrate (PTSA, 0.54 g, 2.82 mmol, Sigma-Aldrich) was added to form a reaction mixture. The ice bath was removed and the reaction mixture was stirred at a temperature of about 25° C. for 16 hrs. Thereafter, the mixture was cooled with an ice bath, treated with saturated aqueous sodium bicarbonate, and extracted with EtOAc. The organic layer was separated, washed with brine, dried (Na2SO4), and concentrated to provide 5.65 g of 114 as an oil (87% yield). 1H NMR (CDCl3) δ: 1.48 (3H, s), 1.54 (3H, s), 3.71 (1H, m), 4.37 (1H, m), 5.11 (1H, t, J=6.76 Hz), 7.53 (1H, dd, J=1.93, 8.63 Hz), 8.18 (1H, d, J=1.88 Hz). LC/MS (M+1): m/z=232.

Workup

  1. temperaturewas cooled with an ice bath
  2. customto form a reaction mixture
  3. customThe ice bath was removed
  4. temperatureThereafter, the mixture was cooled with an ice bath
  5. additiontreated with saturated aqueous sodium bicarbonate
  6. extractionextracted with EtOAc
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-01a72fd35e4a456cb2444b5b1b726aa4
Source dataset
uspto-grants-2016_03
Patent number
US09273043B2

Reaction notes

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