2-Chlorobenzenesulfonyl chloride → {4-[1-(2-Chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid methyl ester

HRID 2363836Notes

Reaction equation

HRID 2363836 reaction equation
C(N(C(C)C)CC)(C)C.FC(F)(F)C(O)=O.[CH3:17][O:18][C:19](=[O:38])[CH2:20][C:21]1[CH:30]=[C:29]([CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([F:37])[CH:27]=2)[CH:22]=1.[Cl:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[S:46](Cl)(=[O:48])=[O:47]>O1CCCC1>[CH3:17][O:18][C:19](=[O:38])[CH2:20][C:21]1[CH:30]=[C:29]([CH:31]2[CH2:36][CH2:35][N:34]([S:46]([C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=3[Cl:39])(=[O:48])=[O:47])[CH2:33][CH2:32]2)[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([F:37])[CH:27]=2)[CH:22]=1

Participants

5

Reactant 3

HCID 761872-Chlorobenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 86686887HCID 86686887, compound

Product 1

HCID 86686897{4-[1-(2-Chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid methyl esterYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diisopropylethylamine (0.6 mL, 3.4 mmol) was added at 0° C. to a solution of (6-fluoro-4-piperidin-4-yl-naphthalen-2-yl)-acetic acid methyl ester trifluoroacetate salt (which may be prepared as described above; 150 mg, 0.36 mmol) in tetrahydrofuran (5 mL), and the mixture was stirred at room temperature for 30 min. 2-Chlorobenzenesulfonyl chloride (available from Sigma-Aldrich; 114 mg, 0.54 mmol) was added and the mixture was stirred at room temperature for 16 h. The solvent was evaporated under reduced pressure. Ethyl acetate was added and the mixture was washed with aqueous NaHCO3 (5 mL) and water (5 mL). The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel using a Biotage purification system, eluting with 10% ethyl acetate/hexanes, to give {4-[1-(2-chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid methyl ester (94 mg, 55%) as a white solid. MS cald. for C24H24ClFNO4S [(M+H)+]: 476, obsd. 476.2.

Workup

  1. stirringthe mixture was stirred at room temperature for 16 h
  2. customThe solvent was evaporated under reduced pressure
  3. additionEthyl acetate was added
  4. washthe mixture was washed with aqueous NaHCO3 (5 mL) and water (5 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel using
  9. customa Biotage purification system
  10. washeluting with 10% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-4d56460210804359a2715117ef32f942
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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