4-Toluenesulfonyl chloride → HCID 178453603, compound

HRID 1984865Notes

Reaction equation

HRID 1984865 reaction equation
[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([CH2:15]O)[CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[N-:29]=[N+:30]=[N-:31].[Na+]>N1C=CC=CC=1.CN(C=O)C>[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([CH2:15][N:29]=[N+:30]=[N-:31])[CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 33557Sodium AzideHCID 178453607HCID 178453607, compound

Product 1

HCID 178453603HCID 178453603, compoundYield 91.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolvent2×HCID 6228DimethylformamideSolvent

Procedure

A solution of trans-(4-hydroxymethyl-cyclohexylmethyl)-carbamic acid tert-butyl ester (123 g, 505 mmol) in pyridine (1 L) was cooled at 4° C. and a solution of p-toluenesulfonyl chloride (125 g, 657 mmol) in pyridine (200 ml) was added below 10° C. The mixture was stirred at ambient temperature for 15 hr and concentrated. After dissolution with EtOAc and H2O, the organic layer was separated. The aqueous layer was extracted with EtOAc (three times), the combined organic layer was washed with H2O, dried over MgSO4, filtered, and concentrated to give a pale yellow oil. To a solution of the above oil in DMF (1.6 L) was added NaN3 (98.8 g, 1.52 mol). The reaction mixture was stirred at ambient temperature for 14 hr and concentrated. After dissolution with CHCl3 and saturated aqueous NaHCO3, the organic layer was separated. The aqueous layer was extracted with CHCl3 (three times), the combined organic layer was dried over MgSO4, filtered, concentrated, and purified by flash chromatography (silica gel, 17% EtOAc in hexane) to give trans-(4-azidomethyl-cyclohexylmethyl)-carbamic acid tert-butyl ester (124 g, 91%) as a colorless oil.

Workup

  1. concentrationconcentrated
  2. dissolutionAfter dissolution with EtOAc and H2O
  3. customthe organic layer was separated
  4. extractionThe aqueous layer was extracted with EtOAc (three times)
  5. washthe combined organic layer was washed with H2O
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a pale yellow oil
  10. stirringThe reaction mixture was stirred at ambient temperature for 14 hr
  11. concentrationconcentrated
  12. dissolutionAfter dissolution with CHCl3 and saturated aqueous NaHCO3
  13. customthe organic layer was separated
  14. extractionThe aqueous layer was extracted with CHCl3 (three times)
  15. dry with materialthe combined organic layer was dried over MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated
  18. custompurified by flash chromatography (silica gel, 17% EtOAc in hexane)

Sources & evidence

ORD record
ord-17457df18e924e35aa1403cbf8e75847
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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