Nitrogen → 4-(4-Fluoro-benzylcarbamoyl)-benzenesulfonyl chloride

HRID 736968Notes

Reaction equation

HRID 736968 reaction equation
[Cl:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9](Cl)=[O:10])=[CH:7][CH:6]=1)(=[O:4])=[O:3].N#N.[F:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][NH2:22])=[CH:19][CH:18]=1.C(N(CC)CC)C>CN(C1C=CN=CC=1)C.C1COCC1>[F:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][NH:22][C:9]([C:8]2[CH:12]=[CH:13][C:5]([S:2]([Cl:1])(=[O:4])=[O:3])=[CH:6][CH:7]=2)=[O:10])=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 8471TriethylamineHCID 673264-FluorobenzylamineHCID 820244-(Chlorosulphonyl)benzoyl chloride

Product 1

HCID 589751254-(4-Fluoro-benzylcarbamoyl)-benzenesulfonyl chlorideYield 80%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Add 4-chlorosulfonyl-benzoyl chloride (103 g (0.433 mol) and anhydrous THF (1.2 L) to a 5-L 3-neck round bottom equipped with overhead stirrer, dropping funnel, N2 line, and temperature probe and cool to −78° C. Add to the stirring solution dropwise over 4 h a solution of 4-fluorobenzylamine (52 g, 0.416 mol), triethylamine (42 g, 0.415 mol), and 4-DMAP (5.3 g, 0.043 mol) in dry THF (1.2 L). Slowly bring to room temperature the resulting mixture and stir overnight. Filter the solids, back-wash with THF, and concentrate the filtrate to a solid. Partion the solid between 1N HCl (1 L) and ethyl acetate (2×1 L). Combine the organics, dry over magnesium sulfate, filter, and concentrate to a solid. Suspend the solid in methyl t-butyl ether (1 L), stir at room temperature for 2 h, filter, and back-wash with ethyl ether (500 mL). Dry the resulting white powder (20 mm Hg, 40° C.) to give 4-(4-fluoro-benzylcarbamoyl)-benzenesulfonyl chloride as a white solid (108.5 g, 80%): 1HNMR (DMSO-d6) δ 9.07 (t, J=5.9 Hz, 1H), 7.82 (d, J=8.3 Hz, 2H), 7.65 (d, J=7.8 Hz, 2H), 7.35 (m, 2H), 7.14 (t, J=8.8 Hz, 2H), 4.44 (d, J=5.9 Hz, 2H); MS (ESI) m/z 326 (m−H); HPLC, 93.6%.

Workup

  1. customequipped with overhead stirrer
  2. customSlowly bring to room temperature
  3. filtrationFilter the solids
  4. washback-wash with THF
  5. concentrationconcentrate the filtrate to a solid
  6. dry with materialCombine the organics, dry over magnesium sulfate
  7. filtrationfilter
  8. concentrationconcentrate to a solid
  9. stirringstir at room temperature for 2 h
  10. filtrationfilter
  11. washback-wash with ethyl ether (500 mL)
  12. customDry the resulting white powder (20 mm Hg, 40° C.)

Sources & evidence

ORD record
ord-1093a1bf4f3141049b56f0fa72774514
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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