Methyl iodide → HCID 58088354, compound

HRID 250292Notes

Reaction equation

HRID 250292 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[CH:13]1([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][C:28]([F:31])([F:30])[F:29])[C:17]=2[CH2:32][O:33][C:34]2[CH:39]=[CH:38][C:37]([C:40]3[CH:41]=[CH:42][C:43]4[C:47]([C:48]([OH:50])=[O:49])=[CH:46][S:45][C:44]=4[CH:51]=3)=[C:36]([CH3:52])[CH:35]=2)[CH2:15][CH2:14]1.CI.[Cl-].[NH4+]>C1COCC1.O.C(OCC)(=O)C>[CH:13]1([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][C:28]([F:29])([F:30])[F:31])[C:17]=2[CH2:32][O:33][C:34]2[CH:39]=[CH:38][C:37]([C:40]3[CH:41]=[CH:42][C:43]4[C:47]([C:48]([OH:50])=[O:49])=[C:46]([CH3:1])[S:45][C:44]=4[CH:51]=3)=[C:36]([CH3:52])[CH:35]=2)[CH2:15][CH2:14]1

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 24752023HCID 24752023, compoundHCID 178418339Butyllithium

Product 1

HCID 58088354HCID 58088354, compoundYield 21.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (120 μL, 0.849 mmol) and THF (4 mL) is cooled to −78° C. A solution of n-butyl lithium (1.6 M in hexanes, 487 μL, 0.779 mmol) is added dropwise and the reaction is stirred for 40 minutes at −78° C. A solution of 6-{4-[5-cyclopropyl-3-(2-trifluoromethoxy-phenyl)-isoxazol-4-ylmethoxy]-2-methyl-phenyl}-benzo[b]thiophene-3-carboxylic acid (200 mg, 0.354 mmol) in THF (2 mL) is added dropwise and the resulting yellow solution is stirred at −78° C. for one hour. Methyl iodide (221 μL, 3.54 mmol) is added dropwise and the reaction is allowed to gradually warm to ambient temperature overnight. The flask is cooled in an ice bath and saturated aqueous ammonium chloride (5 mL) is added. The mixture is diluted with water and ethyl acetate. The ethyl acetate layer is washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue is purified via radial chromatography eluting with 2% MeOH—CH2Cl2. The purification is repeated for impure fractions containing product. The title compound (44 mg, 21%) is obtained as a gray solid.

Workup

  1. stirringthe resulting yellow solution is stirred at −78° C. for one hour
  2. temperatureto gradually warm to ambient temperature overnight
  3. temperatureThe flask is cooled in an ice bath
  4. washThe ethyl acetate layer is washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified via radial chromatography
  8. washeluting with 2% MeOH—CH2Cl2
  9. customThe purification
  10. additioncontaining product

Sources & evidence

ORD record
ord-171d821d6434438aa07327f99b661081
Source dataset
uspto-grants-2011_01
Patent number
US07863302B2

Reaction notes

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