Sodium Azide → tert-Butyl ((trans-4-(((benzyloxy)carbonyl)amino)cyclohexyl)methyl)carbamate

HRID 2085422Notes

Reaction equation

HRID 2085422 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=O.[C:7]([O:11][C:12]([NH:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH:19](C(O)=O)[CH2:18][CH2:17]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[N-]=[N+]=[N-].[Na+]>C1(C)C=CC=CC=1>[C:7]([O:11][C:12]([NH:14][CH2:15][CH:16]1[CH2:17][CH2:18][CH:19]([NH:14][C:12](=[O:11])[O:5][CH2:1][C:2]2[CH:20]=[CH:21][CH:16]=[CH:17][CH:18]=2)[CH2:20][CH2:21]1)=[O:13])([CH3:8])([CH3:9])[CH3:10]

Participants

5

Reactant 3

HCID 33557Sodium AzideHCID 65578Oxalyl chlorideHCID 736918(1r,4r)-4-((((Tert-butoxy)carbonyl)amino)methyl)cyclohexane-1-carboxylic acid

Product 1

HCID 22254006tert-Butyl ((trans-4-(((benzyloxy)carbonyl)amino)cyclohexyl)methyl)carbamate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Oxalyl chloride (1.1 equivalents) was added dropwise to a mixture of 4-[[(tert-butoxycarbonyl)-amino]methyl]-cyclohexanecarboxylic acid (1 equivalent, Maybridge) in toluene. The reaction mixture was stirred at room temperature for 2-6 h. The solvent was removed in vacuo, the residue was dissolved in acetone and the resulting mixture was added dropwise to an aqueous solution of sodium azide (1.2 equivalents) at a rate such as to maintain a temperature of 10-15° C. After the completion of the reaction, the reaction mixture was extracted with ethyl acetate, the combined extracts were dried and concentrated in vacuo. The residue was dissolved in acetone and added slowly to warm (60° C.) benzene. After the completion of the reaction, benzyl alcohol was added to the reaction mixture, stirred for 2 days and the desired product was isolated (For Typical References, See: G. Schroeter Ber. 1909, 42, 3356; and Allen, C. F. H.; Bell, A. Org. Syn. Coll. Vol. 3 (1955) 846.).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in acetone
  3. temperatureto maintain a temperature of 10-15° C
  4. customAfter the completion of the reaction
  5. extractionthe reaction mixture was extracted with ethyl acetate
  6. customthe combined extracts were dried
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in acetone
  9. additionadded slowly
  10. temperatureto warm (60° C.) benzene
  11. customAfter the completion of the reaction, benzyl alcohol
  12. additionwas added to the reaction mixture
  13. stirringstirred for 2 days

Sources & evidence

ORD record
ord-db7f3bf580dc48aaa982965b276b8176
Source dataset
uspto-grants-2004_04
Patent number
US06720324B2

Reaction notes

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