HCID 1948, compound → HCID 12114673, compound

HRID 1858952Notes

Reaction equation

HRID 1858952 reaction equation
[C:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([NH:22][CH2:23][C:24]([OH:26])=O)(=[O:21])=[O:20])=[CH:15][CH:14]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.[CH2:52]([O:59][NH2:60])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>O1CCCC1>[C:53]1([CH2:52][O:59][NH:60][C:24](=[O:26])[CH2:23][NH:22][S:19]([C:16]2[CH:15]=[CH:14][C:13]([N:10]3[CH2:9][CH2:8][CH:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH2:12][CH2:11]3)=[CH:18][CH:17]=2)(=[O:20])=[O:21])[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1

Participants

6

Reactant 4

HCID 1948HCID 1948, compoundHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 102313O-Benzylhydroxylamine

Product 1

HCID 12114673HCID 12114673, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

In a separate flask containing a cool (5° C.), stirred solution of [4-(4-phenyl-piperidin-1-yl)-benzenesulfonylamino]-acetic acid (0.2307 g, 0.0006161 mol) and 1-hydroxy-benzo-1,2,3-triazole (0.0842 g, 0.000623 mol) in anhydrous tetrahydrofuran (10 mL) was added in one portion 1,3-dicyclohexyl-carbodiimide (0.1449 g, 0.000702 mol). The mixture was stirred for 30 minutes at 5° C. then allowed to warm to room temperature. After 3 hours at room temperature, the mixture was added in one portion to the filtrate containing O-benzylhydroxylamine. The mixture was stirred at room temperature for 16 hours, then refluxed (74° C.) for 1 hour. The volatiles were rotary evaporated off, and the residue was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The organics were combined, washed with 0.1 M NaOH, water, 0.1 M HCl, water, and saturated sodium chloride. The organic layer was dried (MgSO4) and rotary evaporated. The residue was dissolved in chloroform, and chromatographed on silica gel (34 g, 230-400 mesh) eluting with dichloromethane-acetone (9:1, 10×30 mL). Fractions containing product were rotary evaporated to give a white solid. The solid was dried in vacuo; yield 0.1448 g (49%), mp=163-165° C.

Workup

  1. additionIn a separate flask containing
  2. temperatureto warm to room temperature
  3. waitAfter 3 hours at room temperature
  4. additionthe mixture was added in one portion to the filtrate
  5. stirringThe mixture was stirred at room temperature for 16 hours
  6. temperaturerefluxed (74° C.) for 1 hour
  7. customThe volatiles were rotary evaporated off
  8. customthe residue was partitioned between ethyl acetate and water
  9. extractionThe aqueous layer was extracted with ethyl acetate
  10. washwashed with 0.1 M NaOH, water, 0.1 M HCl, water, and saturated sodium chloride
  11. dry with materialThe organic layer was dried (MgSO4) and rotary evaporated
  12. dissolutionThe residue was dissolved in chloroform
  13. customchromatographed on silica gel (34 g, 230-400 mesh)
  14. washeluting with dichloromethane-acetone (9:1, 10×30 mL)
  15. additionFractions containing product
  16. customwere rotary evaporated
  17. customto give a white solid
  18. customThe solid was dried in vacuo

Sources & evidence

ORD record
ord-a0032629db6f4c549b1049797e049fad
Source dataset
uspto-grants-2000_11
Patent number
US06153612

Reaction notes

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