Pyridine → Trifluoro-methanesulfonic acid 2-(3-benzyloxy-propoxy)-4-chloro-6-formyl-phenyl ester

HRID 2367998Notes

Reaction equation

HRID 2367998 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]([OH:22])=[C:15]([CH:18]=[C:19]([Cl:21])[CH:20]=1)[CH:16]=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[O:29](S(C(F)(F)F)(=O)=O)[S:30]([C:33]([F:36])([F:35])[F:34])(=O)=[O:31]>C(Cl)Cl>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:20]=[C:19]([Cl:21])[CH:18]=[C:15]([CH:16]=[O:17])[C:14]=1[O:22][S:30]([C:33]([F:36])([F:35])[F:34])(=[O:31])=[O:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 866647393-(3-Benzyloxy-propoxy)-5-chloro-2-hydroxy-benzaldehyde

Product 1

HCID 87109762Trifluoro-methanesulfonic acid 2-(3-benzyloxy-propoxy)-4-chloro-6-formyl-phenyl esterYield 51.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-(3-benzyloxy-propoxy)-5-chloro-2-hydroxy-benzaldehyde (5.3 g, 16.6 mmol) and pyridine (3.4 mL, 41.5 mmol) in CH2Cl2 (70 mL) at 0° C. was added Tf2O (3.1 mL, 18.3 mmol) drop-wise over 5 minutes period and the reaction mixture was stirred for 3 h at room temperature. The solution was diluted with CH2Cl2 (100 mL), washed with water, brine, dried over Na2SO4, then concentrated under reduced pressure. The product was purified by silica gel column chromatography (2:1 hexanes-EtOAc mobile phase) generating the title compound (3.8 g, 8.5 mmol, 51%) as a light yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.18 (s, 1H), 7.48 (d, J=2.3 Hz, 1H), 7.37-7.29 (m, 6H), 4.52 (s, 2H), 4.23 (t, J=6.2 Hz, 2H), 3.69 (t, J=5.8 Hz, 2H), 2.16 (t, J=6.0 Hz, 2H); 19F NMR (376 MHz, CHLOROFORM-d) δ ppm −73.23 (s).

Workup

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe product was purified by silica gel column chromatography (2:1 hexanes-EtOAc mobile phase)

Sources & evidence

ORD record
ord-e657c9a9619b426cbce0c666ebdaf904
Source dataset
uspto-grants-2014_04
Patent number
US08703742B2

Reaction notes

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