Triethylamine → (S)-tert-butyl (2-azido-1-(3-fluoro-5-iodophenyl)ethyl)carbamate

HRID 595999Notes

Reaction equation

HRID 595999 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:10]O)[CH:5]=[C:6]([I:8])[CH:7]=1.CCN(CC)CC.CS(Cl)(=O)=O.[N-:32]=[N+:33]=[N-:34].[Na+]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O.O>[N:32]([CH2:10][C@@H:9]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:4]1[CH:5]=[C:6]([I:8])[CH:7]=[C:2]([F:1])[CH:3]=1)=[N+:33]=[N-:34]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 118054565(S)-tert-butyl (1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl)carbamate

Product 1

HCID 118054631(S)-tert-butyl (2-azido-1-(3-fluoro-5-iodophenyl)ethyl)carbamateYield 78.6%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(S)-tert-butyl (1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl)carbamate (4.8112 g, 12.62 mmol) was dissolved in DCM (100 mL) and cooled to 0° C. Et3N (2.62 mL, 18.93 mmol) was added next and then MsCl (1.180 mL, 15.15 mmol) was added dropwise. The reaction mixture was agitated at same temperature for 30 min after which RM quenched with Sat′d NaHCO3 and water. The product was extracted with DCM and the combined organic layer was dried (magnesium sulfate), filtered and concentrated in vacuo to afford the crude product which was dissolved in DMF (25 mL, ca 0.5 M). NaN3 (2.462 g, 37.9 mmol) was added next and the mixture heated at 70° C. After 6 h, the reaction mixture was cooled to room temperature and diluted with EtOAc and water and the product extracted with EtOAc. The combined organic extract was washed with water thrice and dried (magnesium sulfate), filtered and concentrated in vacuo and the residue purified by flash chromatography (0-50%) EtOAc/heptane to afford 4.03 g of (S)-tert-butyl (2-azido-1-(3-fluoro-5-iodophenyl)ethyl)carbamate as desired product. LCMS (m/z): 351.0 (MH+-56), 1.05 min.

Workup

  1. customquenched with Sat′d NaHCO3 and water
  2. extractionThe product was extracted with DCM
  3. dry with materialthe combined organic layer was dried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford the crude product which
  7. temperaturethe mixture heated at 70° C
  8. waitAfter 6 h
  9. temperaturethe reaction mixture was cooled to room temperature
  10. extractionthe product extracted with EtOAc
  11. extractionThe combined organic extract
  12. washwas washed with water thrice
  13. dry with materialdried (magnesium sulfate)
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customthe residue purified by flash chromatography (0-50%) EtOAc/heptane

Sources & evidence

ORD record
ord-03cadd3bfe8c430b9db0c28e7ccada9f
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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