2,5-Dichlorophenol → Tert-butyl 4-(2-(2,5-dichlorophenoxy)-5-nitrophenylsulfonyl)piperazine-1-carboxylate

HRID 1946851

Reaktionsgleichung

Reaktionsgleichung von HRID 1946851
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[OH:9].[H-].[Na+].Cl[C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:14]=1[S:22]([N:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1)(=[O:24])=[O:23].C1OCCOCCOCCOCCOCCOC1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[O:9][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:14]=1[S:22]([N:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1)(=[O:24])=[O:23]

Komponenten

9

Edukt 5

HCID 662,5-DichlorophenolHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 2855718-Crown-6HCID 59260816Tert-butyl 4-(2-chloro-5-nitrophenylsulfonyl)piperazine-1-carboxylate

Produkt 1

HCID 66770240Tert-butyl 4-(2-(2,5-dichlorophenoxy)-5-nitrophenylsulfonyl)piperazine-1-carboxylateAusbeute 11,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

To a solution of 2,5-dichlorophenol (0.414 g, 2.54 mmol) in THF (20.00 mL) stirred in an ice bath was added NaH (0.101 g, 2.54 mmol) slowly. After addition, the mixture was stirred for 5 min. Compound 38 (0.790 g, 1.95 mmol) was then added and the resulting reaction mixture was heated to 75° C. overnight. The reaction was monitored by HPLC. However, the reaction was not complete after 16 hrs (HPLC), so THF was evaporated and 18-crown-6 (1.057 g, 4.00 mmol), DMF (15 mL), and K2CO3 (0.553 g, 4.00 mmol) were added. The reaction mixture was heated to 100° C. for another 16 hrs, at which time HPLC indicated that the reaction was complete by absence of starting material. The reaction mixture was cooled to room temperature, and water (0.250 mL) was added. The reaction mixture was extracted thrice with EtOAc. Combined extracts were washed sequentially with 1N NaOH, water, and brine, dried over MgSO4, filtered, and evaporated in vacuo. The residual was dissolved in a minimal amount of DCM and purified with chromatography using a gradient of 5 to 30% EtOAc in hexanes. Pure fractions were combined and evaporated in vacuo. The resulting solid was triturated with DCM and hexanes, and then filtered to afford compound 39 as a white/yellow powder (0.120 g, 100% HPLC purity, 10.0% yield). 1H NMR (500 MHz, DMSO-d6): δ 8.59 (d, J=2 Hz, 1H), 8.42 (dd, J1=2 Hz, J2=8 Hz, 1H), 7.76 (d, J=8 Hz, 1H), 7.66 (d, J=3 Hz, 1H), 7.50 (dd, J1=2 Hz, J2=8 Hz, 1H), 7.10 (d, J=8 Hz, 1H), 3.40 (m, 4H), 3.25 (m, 4H), 1.37 (s, 9H).

Aufarbeitung

  1. additionAfter addition
  2. customthe resulting reaction mixture
  3. waitHowever, the reaction was not complete after 16 hrs
  4. custom(HPLC), so THF was evaporated
  5. temperatureThe reaction mixture was heated to 100° C. for another 16 hrs, at which time HPLC
  6. temperatureThe reaction mixture was cooled to room temperature
  7. extractionThe reaction mixture was extracted thrice with EtOAc
  8. washCombined extracts were washed sequentially with 1N NaOH, water, and brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. dissolutionThe residual was dissolved in a minimal amount of DCM
  13. custompurified with chromatography
  14. customevaporated in vacuo
  15. customThe resulting solid was triturated with DCM and hexanes
  16. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-d162dfccb38b4bd09009d2c72c274168
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399456B2

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