Water → (6-Fluoro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester

HRID 1644742Notes

Reaction equation

HRID 1644742 reaction equation
FC(F)(F)S([O:6][S:7]([C:10]([F:13])([F:12])[F:11])(=[O:9])=[O:8])(=O)=O.[CH3:16][O:17][C:18](=[O:33])[CH2:19][C:20]1[C:29]([CH3:30])=[C:28](O)[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([F:32])[CH:26]=2)[CH:21]=1.N1C=CC=CC=1.O>ClCCl>[CH3:16][O:17][C:18](=[O:33])[CH2:19][C:20]1[C:29]([CH3:30])=[C:28]([O:6][S:7]([C:10]([F:11])([F:12])[F:13])(=[O:8])=[O:9])[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([F:32])[CH:26]=2)[CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 59326522(6-Fluoro-4-hydroxy-3-methyl-naphthalen-2-yl)-acetic acid methyl ester

Product 1

HCID 59326772(6-Fluoro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl esterYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Trifluoromethanesulfonic anhydride (0.35 mL, 2.1 mmol) was added drop-wise to a 0° C. solution of (6-fluoro-4-hydroxy-3-methyl-naphthalen-2-yl)-acetic acid methyl ester (400 mg, 1.61 mmol) and pyridine (0.195 mL, 2.42 mmol) in dichloromethane (12.0 mL). The reaction mixture was stirred at 0° C. for 30 minutes. The reaction mixture was warmed to room temperature, and stirred for 4 hours. The reaction mixture was then cooled to 0° C. Water (150 mL) was added, and the mixture was extracted three times with 50 mL portions of dichloromethane. The combined organic layers were dried over Na2SO4, filtered, and evaporated to yield a yellow oil. A solution of this crude product in dichloromethane was evaporated over silica gel, and the resulting silica gel-supported product was subjected to flash chromatography (RediSep® Flash column, 230-400 mesh, 28% ethyl acetate in hexane) to give 514 mg (84%) of (6-fluoro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester as a white, crystalline solid. 1H NMR (300 MHz, CDCl3) δ ppm 7.82 (dd, J=8.9, 5.6 Hz, 1 H), 7.73 (s, 1 H), 7.64 (d, J=10.0 Hz, 1 H), 7.27-7.35 (m, 1 H), 3.84 (s, 2 H), 3.73 (s, 3 H), 2.49 (s, 3 H). HRMS (ES+) cald. for C15H12F4O5S [(M+Na)+] 403.0234, obsd. 403.0233.

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringstirred for 4 hours
  3. temperatureThe reaction mixture was then cooled to 0° C
  4. extractionthe mixture was extracted three times with 50 mL portions of dichloromethane
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto yield a yellow oil
  9. customA solution of this crude product in dichloromethane was evaporated over silica gel

Sources & evidence

ORD record
ord-75cc2d24511e4af5a2d0db483924dd0a
Source dataset
uspto-grants-2012_02
Patent number
US08124629B2

Reaction notes

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