Methyl iodide → HCID 58403371, compound

HRID 1897548Notes

Reaction equation

HRID 1897548 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[C:7]1[NH:8][C:9]3[CH:10]=[C:11]([CH3:16])[CH:12]=[C:13]([CH3:15])[C:14]=3[C:6]=1[CH2:5]2.[OH-].[Na+].I[CH3:23]>C1C=CC=CC=1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[F:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[C:7]1[N:8]([CH3:23])[C:9]3[CH:10]=[C:11]([CH3:16])[CH:12]=[C:13]([CH3:15])[C:14]=3[C:6]=1[CH2:5]2

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 58403403HCID 58403403, compound

Product 1

HCID 58403371HCID 58403371, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 241BenzeneSolvent2×HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 47b (2.74 g, 10.9 mmol) in benzene (59 mL) was added aqueous sodium hydroxide (50% by mass, 5.9 mL), tetrabutylammonium iodide (289 mg, 0.78 mmol), and iodomethane (5.42 mL, 87.1 mmol). The reaction mixture was stirred vigorously at 40° C. for 16 hours and then cooled to room temperature. The mixture was diluted with benzene (20 mL) and H2O (20 mL), and the aqueous layer was extracted 2×20 mL ethyl acetate. Organic layers were combined, washed 1×25 mL H2O, dried over anhydrous magnesium sulfate and concentrated to yield a brown solid. Crude product was purified by flash column chromatography (15:1 hexanes-ethyl acetate followed by a second column 40:1 to 26:1 hexanes-ethyl acetate) to give 48b in 39% yield (1.12 g, 4.24 mmol). 1H NMR (400 MHz, CDCl3): δ 7.51-7.53 (dd, 1H, J=8.2, 5.2 Hz), 7.237-7.260 (m, 1H), 7.99-7.06 (td, 1H, J=9.2, 2.4 Hz), 6.99 (s, 1H), 6.78(s, 1H), 3.97 (s, 3H), 3.80 (s, 2H), 2.60 (s, 3H), 2.46 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 160.5 (d, J=361.5 Hz), 150.4 (d, J=13.5 Hz), 142.42, 141.72, 131.6 (d, J=3.0 Hz), 131.3, 129.0, 121.9, 121.6, 119.5 (d, J=4.5 Hz), 117.1 (d, J=13.5 Hz), 113.2 (d, J=34.5 Hz), 113.5 (d, J=34.1 Hz), 107.1, 31.2 (d, J=2.9 Hz), 30.8, 21.8, 19.0; 19F NMR (CD3CD, 376 MHz): δ −118.0 (m); FTIR: cm−1 3011, 2917, 1588, 1527, 1449, 1417, 1360, 1267, 1212.

Workup

  1. temperaturecooled to room temperature
  2. extractionthe aqueous layer was extracted 2×20 mL ethyl acetate
  3. washwashed 1×25 mL H2O
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. customto yield a brown solid
  7. customCrude product was purified by flash column chromatography (15:1 hexanes-ethyl acetate

Sources & evidence

ORD record
ord-cdca1dfdd1374c29a6b9b1e6d7a1873c
Source dataset
uspto-grants-2013_08
Patent number
US08519122B2

Reaction notes

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