Sodium Iodide → (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-[[iodomethoxy]carbonyloxy]butane

HRID 278401Notes

Reaction equation

HRID 278401 reaction equation
[Na+].[I-:2].[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([C@H:16]([CH3:38])[C@:17]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=3[F:37])([O:24][C:25]([O:27][CH2:28]Cl)=[O:26])[CH2:18][N:19]3[CH:23]=[N:22][CH:21]=[N:20]3)[S:14][CH:15]=2)=[CH:7][CH:6]=1)#[N:4]>CC(C)=O>[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([C@H:16]([CH3:38])[C@:17]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=3[F:37])([O:24][C:25]([O:27][CH2:28][I:2])=[O:26])[CH2:18][N:19]3[CH:23]=[N:22][CH:21]=[N:20]3)[S:14][CH:15]=2)=[CH:7][CH:6]=1)#[N:4]

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 12046103(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-[[chloromethoxy]carbonyloxy]butane

Product 1

HCID 12046104(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-[[iodomethoxy]carbonyloxy]butaneYield 93.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
50 °C

Procedure

NaI (19.4 mmol) was added to an acetone solution of (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-[[chloromethoxy]carbonyloxy]butane (6.5 mmol). The reaction was heated to 50° C. for 5 hours. After cooling to room temperature, the crude reaction was filtered, concentrated, and then dissolved in EtOAc. The organic layer was washed sequentially with aqueous solutions of NaHCO3 and Na2S2O3. The organic layer was then washed with H2O, dried over MgSO4, and was concentrated to obtain 3.76 g of the subtitled compound as a yellow solid. 1H NMR (DMSO) δ8.47 (s, 1H), 8.29 (s, 1H), 8.08 (s, 1H), 7.97 (d, 2H, J=8), 7.88 (d, 2H, J=8), 7.26-7.12 (m, 3H), 6.08 (s, 2H), 5.70 (d, J=1H, J=15), 5.36 (d, 1H, J=15), 4.02 (q, 1H, J=7), and 1.48 (d, 3H, J=7); MS (MH+=622).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe crude reaction
  3. filtrationwas filtered
  4. concentrationconcentrated
  5. dissolutiondissolved in EtOAc
  6. washThe organic layer was washed sequentially with aqueous solutions of NaHCO3 and Na2S2O3
  7. washThe organic layer was then washed with H2O
  8. dry with materialdried over MgSO4
  9. concentrationwas concentrated

Sources & evidence

ORD record
ord-e1117db5123447e1b5e09e47243285e2
Source dataset
uspto-grants-2002_03
Patent number
US06359141B2

Reaction notes

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