Methyl iodide → HCID 76462376, compound

HRID 1972521Notes

Reaction equation

HRID 1972521 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([OH:30])([C:26]([F:29])([F:28])[F:27])[C:22]([F:25])([F:24])[F:23])=[CH:17][C:16]=2[C:31]#[C:32][CH:33]([OH:36])[CH2:34][CH3:35])[CH2:11][CH2:10]1)(=[O:8])=[O:7].[H-].[Na+].[CH3:39]I>C1COCC1>[F:28][C:26]([F:27])([F:29])[C:21]([C:18]1[CH:19]=[CH:20][C:15]([N:12]2[CH2:13][CH2:14][N:9]([S:6]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)(=[O:8])=[O:7])[CH2:10][CH2:11]2)=[C:16]([C:31]#[C:32][CH:33]([O:36][CH3:39])[CH2:34][CH3:35])[CH:17]=1)([OH:30])[C:22]([F:25])([F:23])[F:24]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86670380HCID 86670380, compound

Product 1

HCID 76462376HCID 76462376, compoundYield 82.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(2-(4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-1-pentyn-3-ol (186 mg, 0.33 mmol, Example 154) in dry THF (5 mL) at room temperature was added sodium hydride (60% dispersion in mineral oil, 134 mg, 3.34 mmol). The reaction mixture was stirred at room temperature for 10 min then methyl iodide (0.21 mL, 3.34 mmol) was added. After stirring for an additional 2 h, the solvent was removed under reduced pressure. The crude material was absorbed onto a plug of silica gel and purified by column chromatography (12 g of silica gel, 10 to 30% ethyl acetate in hexanes), to provide 1,1,1,3,3,3-hexafluoro-2-(3-(3-methoxy-1-pentyn-1-yl)-4-(4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (156 mg) as an off-white solid.

Workup

  1. stirringAfter stirring for an additional 2 h
  2. customthe solvent was removed under reduced pressure
  3. customThe crude material was absorbed onto a plug of silica gel
  4. custompurified by column chromatography (12 g of silica gel, 10 to 30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e41b1837a34b4106931e9ce7fc3722f0
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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