m-Bromobenzenesulphonyl chloride → (S)-tert-butyl 4-(3-bromophenylsulfonyl)-3-methylpiperazine-1-carboxylate

HRID 2386566Notes

Reaction equation

HRID 2386566 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([S:8](Cl)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[CH3:12][C@@H:13]1[NH:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1.C(N(C(C)C)CC)(C)C.BrC1C=CC=CC=1S(Cl)(=O)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([S:8]([N:18]2[CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][C@@H:13]2[CH3:12])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 17943m-Bromobenzenesulphonyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 5204032-Bromobenzenesulfonyl chlorideHCID 7023035(S)-1-Boc-3-methylpiperazine

Product 1

HCID 67044958(S)-tert-butyl 4-(3-bromophenylsulfonyl)-3-methylpiperazine-1-carboxylateYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

3-bromobenzene-1-sulfonyl chloride and (S)-tert-butyl 3-methylpiperazine-1-carboxylate was coupled following as follows: Dissolve 1 g (5 mmol) of the amine in 10 mL of methylene chloride. Add 2.0 eq. of diisopropyl ethylamine. Cool to 0° C. and add 1.5 equivalents of bromobenzene sulfonyl chloride dropwise (ca. 1 min) and stir for 5 min. Warm to rt and stir for an additional 16 h. Work up by adding a saturated solution of NaHCO3 and extracting with EtOAc. Wash the organic layer with HCl (1 N) followed by NaHCO3 and brine. Remove the solvent to afford crude, yellow oil. Purification of the sulfonamide derivative by Biotage on silica gel (99% MeOH/DCM) affords the desired product as a yellow oil. The yield was 55%. LC-MS showed the product was >95% pure and had the expected M+H+ of 420. 1H NMR (Varian 300 MHz, CDCl3, shifts relative to the solvent peak at 7.24 ppm) δ 7.9 (d, 1H) 7.72-7.65 (m, 2H) 7.4 (t, 1H), 3.7 (m, 2H) 3.6 (m, 1H), 3.13-3.0 (m, 2H) 2.92-2.77 (m, 2H), 1.4 (s, 12H) 1.0 (d, 3H).

Workup

  1. temperatureWarm to rt
  2. stirringstir for an additional 16 h
  3. extractionextracting with EtOAc
  4. washWash the organic layer with HCl (1 N)
  5. customRemove the solvent
  6. customto afford crude, yellow oil
  7. customPurification of the sulfonamide derivative by Biotage on silica gel (99% MeOH/DCM)

Sources & evidence

ORD record
ord-6798c97c0dce4f12b21b27cfcc39b060
Source dataset
uspto-grants-2012_09
Patent number
US08268822B2

Reaction notes

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