Methyl iodide → HCID 67351679, compound

HRID 2369232Notes

Reaction equation

HRID 2369232 reaction equation
[F:1][C:2]1[CH:19]=[C:18]2[C:5]([CH2:6][C:7]3[C:15]4[CH:14]=[CH:13][C:12]([O:16][CH3:17])=[CH:11][C:10]=4[NH:9][C:8]=32)=[CH:4][CH:3]=1.[OH-].[Na+].I[CH3:23]>C1C=CC=CC=1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[F:1][C:2]1[CH:19]=[C:18]2[C:5]([CH2:6][C:7]3[C:15]4[CH:14]=[CH:13][C:12]([O:16][CH3:17])=[CH:11][C:10]=4[N:9]([CH3:23])[C:8]=32)=[CH:4][CH:3]=1.[F:1][C:2]1[CH:19]=[C:18]2[C:5]([CH2:6][C:7]3[C:15]4[CH:14]=[CH:13][C:12]([O:16][CH3:17])=[CH:11][C:10]=4[NH:9][C:8]=32)=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 67353502HCID 67353502, compound

Product 2

HCID 67351679HCID 67351679, compoundHCID 67353502HCID 67353502, compound

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 241BenzeneSolvent2×HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 55 (as a 3:1 mixture of regioisomers, 1.26 g, 4.98 mmol) in benzene (25 mL) was added aqueous sodium hydroxide (50% by mass, 3 mL), tetrabutylammonium iodide (152.1 mg, 0.41 mmol), and iodomethane (2.48 mL, 39.8 mmol). The reaction mixture was stirred vigorously at 40° C. for 17 hours and then cooled to room temperature over 3.5 hours. 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. Crude product was purified by flash column chromatography (40:1 hexanes-ethyl acetate) to give 56 as one regioisomer in 71% yield (713 mg, 2.67 mmol, % yield based on amount of 55 in starting material mixture). 1H NMR (600 MHz, CDCl3): δ 7.49 (d, 1H, J=9 Hz), 7.37-7.39 (dd, 1H, J=7.8 Hz, 4.8 Hz), 7.21-7.23 (dd, 1H, J=9.3 Hz, 1.8 Hz), 6.82-6.86 (m, 3H), 3.92 (s, 3H), 3.91 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 162.2 (d, J=240 Hz), 156.4, 142.8, 142.7 (d, J=3 Hz), 142.6 (d, J=3 Hz), 137.1 (d, J=9.5 Hz), 125.8 (d, J=9.2 Hz), 122.4, 119.8, 118.4, 109.9 (d, J=22.5 Hz), 109.3, 104.3 (d, J=24.8 Hz), 93.7, 55.7, 30.9, 29.5; 19F NMR (CD3CD, 376 MHz): δ −116.0 (q, J=14.1, 9.4 Hz); FTIR: cm−1 1611, 1592, 1530, 1460, 1380, 1258, 1221, 1161. EI-HRMS: Calcd. for C17H14FNO+ [M]+: 267.1059. found 267.1062.

Workup

  1. temperaturecooled to room temperature over 3.5 hours
  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. customCrude product was purified by flash column chromatography (40:1 hexanes-ethyl acetate)

Sources & evidence

ORD record
ord-c4af08b731a24471b62d0a6551521b0e
Source dataset
uspto-grants-2014_04
Patent number
US08703936B2

Reaction notes

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