Phenylmethanesulfonyl chloride → HCID 86686910, compound

HRID 2363862Notes

Reaction equation

HRID 2363862 reaction equation
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:30])[CH2:11][C:12]1[C:21]([CH3:22])=[C:20]([CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([F:29])[CH:18]=2)[CH:13]=1.C(N(CC)C(C)C)(C)C.[C:40]1([CH2:46][S:47](Cl)(=[O:49])=[O:48])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(Cl)Cl>[CH3:8][O:9][C:10](=[O:30])[CH2:11][C:12]1[C:21]([CH3:22])=[C:20]([CH:23]2[CH2:24][CH2:25][N:26]([S:47]([CH2:46][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)(=[O:49])=[O:48])[CH2:27][CH2:28]2)[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([F:29])[CH:18]=2)[CH:13]=1

Participants

5

Reactant 3

HCID 74740Phenylmethanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 86686889HCID 86686889, compound

Product 1

HCID 86686910HCID 86686910, compoundYield 79.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of (6-fluoro-3-methyl-4-piperidin-4-yl-naphthalen-2-yl)-acetic acid methyl ester trifluoroacetate salt (which may be prepared as described above; 102 mg, 0.237 mmol) and N,N-diisopropylethylamine (124 μL, 0.711 mmol) in methylene chloride (6.0 mL) was added α-toluenesulfonyl chloride (90.4 mg, 0.474 mmol). After stirring for ˜10 minutes at 0° C., the light yellow reaction mixture was allowed to warm to room temperature and then stirred for 4 hours at room temperature under nitrogen. During this time, some solvent had evaporated. The reaction mixture was diluted with water (˜25 mL) and extracted with methylene chloride (3×25 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered, concentrated, and purified by silica gel chromatography (eluting with 33% ethyl acetate/hexanes) to give [6-fluoro-3-methyl-4-(1-phenylmethanesulfonyl-piperidin-4-yl)-naphthalen-2-yl]-acetic acid methyl ester (88 mg, 79%). MS cald. for C26H29FNO4S [(M+H)+]: 470, obsd. 470.2.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 4 hours at room temperature under nitrogen
  3. customDuring this time, some solvent had evaporated
  4. additionThe reaction mixture was diluted with water (˜25 mL)
  5. extractionextracted with methylene chloride (3×25 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography (eluting with 33% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e57633963f474c09831daf2c11b5c35c
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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