Water → HCID 59350831, compound

HRID 1644745Notes

Reaction equation

HRID 1644745 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:40])[CH2:19][C:20]1[C:29]([CH3:30])=[C:28]([CH2:31][C:32]2[CH:37]=[CH:36][C:35](O)=[CH:34][CH:33]=2)[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([F:39])[CH:26]=2)[CH:21]=1.N1C=CC=CC=1.O>ClCCl>[CH3:16][O:17][C:18](=[O:40])[CH2:19][C:20]1[C:29]([CH3:30])=[C:28]([CH2:31][C:32]2[CH:33]=[CH:34][C:35]([O:6][S:7]([C:10]([F:11])([F:12])[F:13])(=[O:8])=[O:9])=[CH:36][CH:37]=2)[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([F:39])[CH:26]=2)[CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 59350800HCID 59350800, compound

Product 1

HCID 59350831HCID 59350831, compoundYield 70.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoromethanesulfonic anhydride (2.6 mL, 15.0 mmol) was added drop-wise to a -6° C. solution of [6-fluoro-4-(4-hydroxy-benzyl)-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (3.9 g, 11.5 mmol) and pyridine (1.4 mL, 17.4 mmol) in dichloromethane (100 mL). The reaction mixture was warmed to room temperature, and stirred for 1 hour. The reaction mixture was then cooled to 4° C. Water (20 mL) was added, and the organic layer was dried over MgSO4, filtered, and concentrated. A solution of this crude product in dichloromethane was concentrated over silica gel, and the resulting silica gel-supported product was subjected to flash chromatography (Analogix SuperFlash™ column, 5%-20% ethyl acetate in hexane) to give 3.8 g (70%) of [6-fluoro-3-methyl-4-(4-trifluoromethanesulfonyloxy-benzyl)-naphthalen-2-yl]-acetic acid methyl ester as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.94 (dd, J=8.9, 6.2 Hz, 1 H), 7.79 (s, 1 H), 7.70 (dd, J=12.1, 1.8 Hz, 1 H), 7.37 (d, J=8.8 Hz, 2 H), 7.29-7.38 (m, 1 H), 7.20 (d, J=8.8 Hz, 2 H), 4.53 (s, 2 H), 3.94 (s, 2 H), 3.64 (s, 3 H), 2.29 (s, 3 H).

Workup

  1. temperatureThe reaction mixture was then cooled to 4° C
  2. dry with materialthe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. concentrationA solution of this crude product in dichloromethane was concentrated over silica gel

Sources & evidence

ORD record
ord-eda43e08505a46489380e7f1c009a213
Source dataset
uspto-grants-2012_02
Patent number
US08124629B2

Reaction notes

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