1-Butanaminium, N,N,N-tributyl-, azide → Tert-butyl 4-azido-3,3-difluoropyrrolidine-1-carboxylate

HRID 928200Notes

Reaction equation

HRID 928200 reaction equation
[F:1][C:2]1([F:22])[CH:6](OS(C(F)(F)F)(=O)=O)[CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3]1.[N-:23]=[N+:24]=[N-:25].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C=O)C.CC(OC)(C)C>[N:23]([CH:6]1[CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3][C:2]1([F:22])[F:1])=[N+:24]=[N-:25]

Participants

5

Reactant 2

HCID 57432321-Butanaminium, N,N,N-tributyl-, azideHCID 118073690Tert-butyl 3,3-difluoro-4-{[(trifluoromethyl)sulfonyl]oxy}pyrrolidine-1-carboxylate

Product 1

HCID 90158699Tert-butyl 4-azido-3,3-difluoropyrrolidine-1-carboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

tert-Butyl 3,3-difluoro-4-{[(trifluoromethyl)sulfonyl]oxy}pyrrolidine-1-carboxylate (5.56 g, 15.2 mmol) was dissolved in DMF (20 mL) and cooled in an ice bath under nitrogen atmosphere. Tetrabutylammonium azide (TBA-N3, 4.8 g, 17 mmol, 1.1 mol eq) in DMF (15 mL) was added slowly over 15 min via an addition funnel. The reaction mixture was stirred in the cold bath and was allowed to warm to ambient temperature gradually. After 16 hr, the reaction was diluted with MTBE (300 mL), washed with sat. aq. NaHCO3 (2×30 mL), and brine (2×30 mL), dried over Na2SO4 and evaporated to give a residue. This crude material was purified on silica (40 g) with gradients from 100% heptane to 20% ethyl acetate-80% heptane to give the title product as a colorless oil (3.02 g, 80% yield, >95% purity). 1H NMR (400 MHz, chloroform-d) δ ppm 4.06 (dtd, J=8.86, 5.41, 5.41, 3.91 Hz, 1 H) 3.65-3.83 (m, 3 H) 3.36-3.57 (m, 1 H) 1.47 (s, 9 H). 19F NMR (376 MHz, chloroform-d) δ ppm −106.10-−102.44 (m, 1 F) −120.14-−116.68 (m, 1 F). m/z (ESI+) for C9H14F2N4O2 149 (small)/123 (M+H)+.

Workup

  1. temperaturecooled in an ice bath under nitrogen atmosphere
  2. washwashed with sat. aq. NaHCO3 (2×30 mL), and brine (2×30 mL)
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customto give a residue
  6. customThis crude material was purified on silica (40 g) with gradients from 100% heptane to 20% ethyl acetate-80% heptane

Sources & evidence

ORD record
ord-c736d476b93f4bfda25d25c120ae0476
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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