Sodium Azide → HCID 59371519, compound

HRID 2095364Notes

Reaction equation

HRID 2095364 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[C:16]([CH2:20][CH2:21][C:22]2[CH:23]=[C:24]([CH2:28]Cl)[CH:25]=[CH:26][CH:27]=2)[CH:17]=[N:18][CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:30]=[N+:31]=[N-:32].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[C:16]([CH2:20][CH2:21][C:22]2[CH:23]=[C:24]([CH2:28][N:30]=[N+:31]=[N-:32])[CH:25]=[CH:26][CH:27]=2)[CH:17]=[N:18][CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 33557Sodium AzideHCID 59371458HCID 59371458, compound

Product 1

HCID 59371519HCID 59371519, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-[2-[5-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]ethyl]phenylmethyl chloride is dissolved in DMF, and sodium azide (1-4 equiv.) is added. The reaction mixture is stirred with exclusion of moisture at ambient or elevated temperature until all starting material has been converted. The solvent is then distilled into a cooled receiver in an oil pump vacuum at a bath temperature of up to 40° C. (caution should be observed not to exceed this temperature, as organic azides may explode upon heating). The residue is diluted with EtOAc and water, and the phases are separated. The organic phase is washed with brine, dried over MgSO4, and evaporated, and the residue is chromatographed on silica gel with EtOAc or a mixture of EtOAc with a nonpolar solvent. Evaporation of the product-containing fractions and drying yields the azide. Before the subsequent step, the azide is preferably evaporated with toluene to remove residual EtOAc, which may react with the amine to be prepared. In order to obtain the following intermediate directly in a form that does not require further purification, it may be convenient to further purify the azide by preparative HPLC (for example, acetonitrile/water gradient on C18).

Workup

  1. distillationThe solvent is then distilled into a cooled receiver in an oil pump vacuum at a bath temperature of up to 40° C. (caution
  2. temperatureupon heating)
  3. additionThe residue is diluted with EtOAc and water
  4. customthe phases are separated
  5. washThe organic phase is washed with brine
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customthe residue is chromatographed on silica gel with EtOAc
  9. additiona mixture of EtOAc with a nonpolar solvent
  10. customEvaporation of the product-containing fractions
  11. customdrying

Sources & evidence

ORD record
ord-deb78f7cab314458991d7ec2cd00fc8d
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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