Sodium Iodide → 4'-Hydroxy-3'-iodo-3-methyl-1,1'-biphenyl-4-carbonitrile
Reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[C:10]([CH3:16])[CH:9]=2)=[CH:4][CH:3]=1.[Na+].[I-:18].[OH-].[Na+]>CO>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[C:10]([CH3:16])[CH:9]=2)=[CH:6][C:7]=1[I:18]Participants
Conditions
- Temperature
- 0 °C
Procedure
The product from Example 106B (4.67 g, 22.3 mmol), NaI (3.343 g, 22.3 mmol), and NaOH (892 mg, 22.3 mmol) were combined in methanol (70 mL) at 0° C. and treated with bleach (5.25%, 31.6 g) dropwise over 30 minutes. After being stirred at 0° C. for 80 minutes, the mixture was quenched with 10% aqueous sodium thiosulfate (10 mL). The mixture was acidified with 1M aqueous HCl (25 mL), neutralized with dipotassium hydrogen phosphate, recooled to 0° C., and filtered. The solids were rinsed with water, then mostly dissolved in 50% EtOAc/hexanes and filtered. When this filtrate was mostly concentrated crystals began to form. The solids were slurried with 20% EtOAc/hexanes, collected by filtration, and washed with 10% EtOAc/hexanes followed by hexanes to provide the impure title compound as a light tan powder (52% yield). MS (ESI APCI negative ion detection) m/z 334 (M−H)−; 1HNMR (300 MHz, d6-DMSO) δ 2.52 (s, 3H), 6.98 (d, 1 H), 7.58-7.63 (m, 2 H), 7.73 (s, 1 H), 7.78 (d, 1 H), 8.06 (d, 1 H), 10.66 (s, 1 H).
Workup
- additiontreated with bleach (5.25%, 31.6 g) dropwise over 30 minutes
- customthe mixture was quenched with 10% aqueous sodium thiosulfate (10 mL)
- customrecooled to 0° C.
- filtrationfiltered
- washThe solids were rinsed with water
- dissolutionmostly dissolved in 50% EtOAc/hexanes
- filtrationfiltered
- customto form
- filtrationcollected by filtration
- washwashed with 10% EtOAc/hexanes
Sources & evidence
- ORD record
- ord-e29b5d5961b641b1a5e0874afddd2148
- Source dataset
- uspto-grants-2005_11
- Patent number
- US06969730B2
Reaction notes
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