Hydrochloric Acid → tert-butyl (3R,4S)-4-hydroxy-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate

HRID 338944Notes

Reaction equation

HRID 338944 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C@@H:8]([N:13]2[CH2:17][C@H:16]([OH:18])[C@H:15]([NH:19][C:20](=[O:29])[O:21]CC3C=CC=CC=3)[CH2:14]2)[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.I[Si](C)(C)C.Cl.[NH2:36][NH2:37]>C(#N)C.C(O)C(C)C>[OH:18][C@H:16]1[CH2:17][N:13]([C@H:8]([C:5]2[CH:6]=[N:7][C:2]([NH:36][NH2:37])=[CH:3][CH:4]=2)[C:9]([F:12])([F:10])[F:11])[CH2:14][C@H:15]1[NH:19][C:20](=[O:29])[O:21][C:5]([CH3:8])([CH3:6])[CH3:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 9321HydrazineHCID 85247Trimethylsilyl iodideHCID 86707466benzyl (3R,4S)-1-((R)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)-4-hydroxypyrrolidin-3-ylcarbamate

Product 1

HCID 86707467tert-butyl (3R,4S)-4-hydroxy-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamateYield 86%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6560IsobutanolSolvent

Procedure

To a solution of benzyl (3R,4S)-1-((R)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)-4-hydroxypyrrolidin-3-ylcarbamate (1.16 g, 2.7 mmol) in acetonitrile (2 mL) cooled to 0° C. in an ice bath was added iodotrimethylsilane (1.22 mL, 8.10 mmol) and the mixture allowed to warm to ambient temperature for 1 hour. The reaction mixture was poured into aqueous 1N HCl (15 mL) and stirred for 10 minutes and extracted with diethyl ether. The aqueous layer was pH adjusted to 10 with a 5N sodium hydroxide solution and extracted with ethyl acetate. The organic extract was dried (MgSO4), filtered and concentrated under reduced pressure. The residue (0.512 g, 1.29 mmol) was combined with anhydrous hydrazine (0.81 mL, 25.87 mmol) in i-BuOH (3 mL) in a sealed tube and heated with stirring at 100° C. for 18 hours. After cooling, the mixture was partitioned between water (15 mL) and ethyl acetate (50 mL). The layers were separated and the organic layer was washed with saturated sodium bicarbonate and brine, dried (MgSO4), filtered and concentrated under reduced pressure to afford tert-butyl (3R,4S)-4-hydroxy-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate (0.44 g, 86%).

Workup

  1. extractionextracted with diethyl ether
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. dry with materialwas dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. temperatureheated
  8. stirringwith stirring at 100° C. for 18 hours
  9. temperatureAfter cooling
  10. customthe mixture was partitioned between water (15 mL) and ethyl acetate (50 mL)
  11. customThe layers were separated
  12. washthe organic layer was washed with saturated sodium bicarbonate and brine
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0a60c7588fbf4e6c90a359e5069d3ff6
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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