2,6-Lutidine → HCID 57947965, compound

HRID 341005Notes

Reaction equation

HRID 341005 reaction equation
[C:1]([O:5][C:6]([O:8][CH2:9][C@@H:10]([N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:11][C:12]([F:16])([F:15])[CH2:13]O)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C(C)=CC=CC=1C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[N-:49]=[N+:50]=[N-:51].[Na+]>C(Cl)Cl>[N:49]([CH2:13][C:12]([F:16])([F:15])[CH2:11][C@H:10]([N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:9][O:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[N+:50]=[N-:51]

Participants

6

Reactant 4

HCID 79372,6-LutidineHCID 33557Sodium AzideHCID 67749Trifluoromethanesulfonic anhydrideHCID 57947907HCID 57947907, compound

Product 1

HCID 57947965HCID 57947965, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of (S)-tert-butyl 1-(tert-butoxycarbonyloxy)-4,4-difluoro-5-hydroxypentan-2-yl(methyl)carbamate (35.3 g, 0.0956 mol) and lutidine (22.2 mL, 0.191 mol) in DCM (300 mL) was added trifluoromethanesulfonic anhydride (19.3 mL, 0.115 mol) at 0° C. The reaction mixture was stirred at 0° C. for 1 h. LC-MS showed the reaction was complete. The reaction mixture was concentrated down. The resulting residue was dissolved in DMF (100 mL) and sodium azide (62.1 g, 0.956 mol) was added. The reaction mixture was stirred at RT overnight. The reaction solution was partitioned between EtOAc and saturated sodium bicarbonate solution. After separating layers, the aqueous layer was extracted further with EtOAc. The combined organic layers were dried (Na2SO4), filtered, and concentrated, and the resulting residue was purified by silica gel column (hexanes/EtOAc) to give (S)-tert-butyl 5-azido-1-(tert-butoxycarbonyloxy)-4,4-difluoropentan-2-yl(methyl)carbamate (0.0956 mol, 100%). LRMS (M+Na+) m/z 417.4.

Workup

  1. concentrationThe reaction mixture was concentrated down
  2. dissolutionThe resulting residue was dissolved in DMF (100 mL)
  3. stirringThe reaction mixture was stirred at RT overnight
  4. customThe reaction solution was partitioned between EtOAc and saturated sodium bicarbonate solution
  5. customAfter separating layers
  6. extractionthe aqueous layer was extracted further with EtOAc
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customthe resulting residue was purified by silica gel column (hexanes/EtOAc)

Sources & evidence

ORD record
ord-55c581c203f547589bb1cb0b1c291036
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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