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

HRID 14968

Reaktionsgleichung

Reaktionsgleichung von HRID 14968
[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

Komponenten

7

Edukt 5

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-5d9911e69edf4398b3d3d8026db17c27
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732444B2

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