2-Fluoro-4-iodoaniline → 1,1-Dimethylethyl ((1S)-1-{[(2-fluoro-4-Iodophenyl)amino]carbonyl}-3-hydroxypropyl)carbamate

HRID 2054541Notes

Reaction equation

HRID 2054541 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[NH2:4].C[Al](C)C.[O:14]=[C:15]1[C@@H:19]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:18][CH2:17][O:16]1>C(Cl)Cl>[F:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[NH:4][C:15]([C@@H:19]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:24])[CH3:26])[CH2:18][CH2:17][OH:16])=[O:14]

Participants

5

Reactant 3

HCID 1856942-Fluoro-4-iodoanilineHCID 688318tert-butyl N-[(3S)-2-oxooxolan-3-yl]carbamateHCID 16682925Trimethylaluminum

Product 1

HCID 588908061,1-Dimethylethyl ((1S)-1-{[(2-fluoro-4-Iodophenyl)amino]carbonyl}-3-hydroxypropyl)carbamateYield 50.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-fluoro-4-iodoaniline (7.11 g) in anhydrous DCM (40 ml) under N2 at 0° C. was treated dropwise with trimethylaluminium (2N in heptane; 15 ml). The mixture was allowed to stir for 30 min before a solution of tert-butyl (3S)-2-oxotetrahydrofuran-3-ylcarbamate (5.03 g), in anhydrous DCM (35 ml), was added dropwise. The reaction was allowed to warm up to ambient temperature and stirred for 18 h, before quenching with 10% aqueous citric acid acid (10 ml) Saturated aqueous potassium sodium tartrate (100 ml) was then added with stirring followed by separation of the organic and aqueous layers. The organic layer was dried (over magnesium sulphate) and concentrated under reduced pressure. The residue was purified using Biotage™ chromatography (silica, eluting with cyclohexane:ethyl acetate 3:2) to afford an off-white solid which was an inseparable mixture (c. 1:2) of the starting material and the title compound (5.55 g).

Workup

  1. additionwas added dropwise
  2. custombefore quenching with 10% aqueous citric acid acid (10 ml) Saturated aqueous potassium sodium tartrate (100 ml)
  3. additionwas then added
  4. stirringwith stirring
  5. customfollowed by separation of the organic and aqueous layers
  6. dry with materialThe organic layer was dried (over magnesium sulphate)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified
  9. washBiotage™ chromatography (silica, eluting with cyclohexane:ethyl acetate 3:2)
  10. customto afford an off-white solid which

Sources & evidence

ORD record
ord-dca085092d714ffc95ee1f58f5201f3b
Source dataset
uspto-grants-2008_02
Patent number
US07329685B2

Reaction notes

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