Hydrochloric Acid → tert-butyl-1-(4-(N-1,2,4-thiadiazol-5-ylsulfamoyl)phenyl)piperidin-4-ylcarbamate

HRID 1715939Notes

Reaction equation

HRID 1715939 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:16][N:15]=[CH:14][N:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:17]([O:21][C:22](=[O:30])[NH:23][CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)([CH3:20])([CH3:19])[CH3:18].P.CC([O-])(C)C.[Na+].Cl>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O.O.C1(C)C=CC=CC=1>[S:16]1[C:12]([NH:11][S:8]([C:5]2[CH:6]=[CH:7][C:2]([N:27]3[CH2:26][CH2:25][CH:24]([NH:23][C:22](=[O:30])[O:21][C:17]([CH3:19])([CH3:18])[CH3:20])[CH2:29][CH2:28]3)=[CH:3][CH:4]=2)(=[O:10])=[O:9])=[N:13][CH:14]=[N:15]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 24404PhosphineHCID 7238334-(N-Boc-amino)piperidineHCID 23676156Sodium t-butoxideHCID 536276064-bromo-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

Product 1

HCID 59465703tert-butyl-1-(4-(N-1,2,4-thiadiazol-5-ylsulfamoyl)phenyl)piperidin-4-ylcarbamateYield 70%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Prepared using general procedure 27. A mixture of 4-bromo-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (3.7 g, 11.6 mmol), tert-butyl-piperidin-4-ylcarbamate (2.32 g, 11.6 mmol), Pd2(dba)3 (319 mg, 0.35 mmol), phosphine (415 mg, 1.39 mmol), NaOtBu (3.55 g, 34.8 mmol) and toluene (30 mL) was stirred at 70° C. for 3 h. After allowing the mixture to cool to RT, H2O (50 mL) and EtOAc (50 mL) were added. After acidifying with a 1 M HCl solution to pH 4, the layers were separated, and the aqueous phase was extracted 3 times with CH2Cl2 (50 mL). The combined organic extracts were dried over MgSO4 and absorbed onto Celite. Purification via silica gel chromatography using 10% MeOH in CH2Cl2 gave tert-Butyl 1-(4-(N-1,2,4-thiadiazol-5-ylsulfamoyl)phenyl)-piperidin-4-ylcarbamate as an off-white foam (357 mg, 70%). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=440.5; tR=2.76 min.

Workup

  1. customPrepared
  2. temperatureto cool to RT
  3. customthe layers were separated
  4. extractionthe aqueous phase was extracted 3 times with CH2Cl2 (50 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. customabsorbed onto Celite
  7. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-1bfa890458314079990a32f29cd6bb9f
Source dataset
uspto-grants-2010_09
Patent number
US07799822B2

Reaction notes

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