Water → 3-Chloro-8-trifluoromethanesulfonyloxy-naphthalene-2-carboxylic acid ethyl ester

HRID 1968758Notes

Reaction equation

HRID 1968758 reaction equation
[F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].[CH2:16]([O:18][C:19]([C:21]1[C:30]([Cl:31])=[CH:29][C:28]2[C:23](=[C:24](O)[CH:25]=[CH:26][CH:27]=2)[CH:22]=1)=[O:20])[CH3:17].O>N1C=CC=CC=1>[CH2:16]([O:18][C:19]([C:21]1[C:30]([Cl:31])=[CH:29][C:28]2[C:23](=[C:24]([O:6][S:3]([C:2]([F:15])([F:14])[F:1])(=[O:5])=[O:4])[CH:25]=[CH:26][CH:27]=2)[CH:22]=1)=[O:20])[CH3:17]

Participants

5

Reactant 3

HCID 962WaterHCID 67749Trifluoromethanesulfonic anhydride2×HCID 66881802Ethyl 3-chloro-8-hydroxynaphthalene-2-carboxylate

Product 1

HCID 866257923-Chloro-8-trifluoromethanesulfonyloxy-naphthalene-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Trifluoromethanesulfonic anhydride (2.46 g, 8.73 mmol, 1.2 equiv) was added at −20° C. under an atmosphere of argon to a solution of 3-chloro-8-hydroxy-naphthalene-2-carboxylic acid ethyl ester (1.82 g, 7.28 mmol) in pyridine (55 ml). After 1 hour at 0° C., an additional portion of trifluoromethanesulfonic anhydride (2.46 g, 8.73 mmol, 1.2 equiv) was added, and stirring was continued at 0° C. for another 1.5 hours. Cold water (4° C., 100 ml) was carefully added, and the reaction mixture was extracted with EtOAc (1 liter in total). The combined organic layers were washed with concentrated aqueous NH4Cl solution and brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (slow gradient of hexane/EtOAc 100:0 to 90:10) afforded the title compound (2.45 g, 88%, inseparable 1:1.3 mixture of regioisomers A:B) as an oil. 1H NMR (400 MHz, CDCl3): δ=8.56 (s, 1H isomer B), 8.40 (s, 1H isomer A), 8.12 (s, 1H isomer A), 8.01 (s, 1H isomer B), 7.93-7.91 (m, 1H isomer A), 7.81 (d, J=8.6 Hz, 1H isomer B), 7.62-7.51 (m, 2H isomer A+2H isomer B), 4.47 (q, J=7.1 Hz, 2H isomer A+2H isomer B), 1.45 (t, J=7.1 Hz, 3H isomer A+3H isomer B). 19F NMR (377 MHz, CDCl3): δ=−73.02. MS (ES+): 383 (M+H)+.

Workup

  1. waitwas continued at 0° C. for another 1.5 hours
  2. extractionthe reaction mixture was extracted with EtOAc (1 liter in total)
  3. washThe combined organic layers were washed with concentrated aqueous NH4Cl solution and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification via flash chromatography (slow gradient of hexane/EtOAc 100:0 to 90:10)

Sources & evidence

ORD record
ord-726c94aa0b444f2d8ddcc5ea3424a253
Source dataset
uspto-grants-2013_04
Patent number
US08426440B2

Reaction notes

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