Methyl iodide → HCID 86653599, compound

HRID 1892007Notes

Reaction equation

HRID 1892007 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:20])[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH2:11][CH:10]([CH2:18][OH:19])[CH2:9]2)=[CH:4][C:3]=1[C:21]([F:24])([F:23])[F:22].[CH3:25]I>CN(C=O)C.C(OCC)(=O)C.[Ag]=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:20])[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH2:11][CH:10]([CH2:18][O:19][CH3:25])[CH2:9]2)=[CH:4][C:3]=1[C:21]([F:22])([F:23])[F:24]

Participants

6

Reactant 2

HCID 6328Methyl iodideHCID 86653598HCID 86653598, compound

Product 1

HCID 86653599HCID 86653599, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 92152Silver(II) oxideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl (4RS,6RS)-6-(4-chloro-3-(trifluoromethyl)phenyl)-4-(hydroxymethyl)-6-methylcyclohex-1-enecarboxylate (Example 7, Step 9; 32.2 mg, 0.089 mmol) in DMF (0.25 mL) was diluted with methyl iodide (0.75 mL, 11.99 mmol) and treated with silver oxide (103 mg, 0.444 mmol). The resulting suspension was protected from ambient light and stirred at rt for 41.5 h. After this time, the mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel, eluting with 10-30% ethyl acetate-hexanes, to provide methyl (4RS,6RS)-6-(4-chloro-3-(trifluoromethyl)phenyl)-4-(methoxymethyl)-6-methylcyclohex-1-enecarboxylate as a colorless gum (20 mg, 60%). Mass spectrum m/z 394.1 (M+NH4+). 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J=2.2 Hz, 1 H), 7.38 (d, J=8.4 Hz, 1 H), 7.31 (dd, J=8.4, 2.2 Hz, 1 H), 7.27 (m, 1 H), 3.64 (s, 3 H), 3.24 (s, 3 H), 3.15 (d, J=5.7 Hz, 2 H), 2.44 (m, 1 H), 2.00 (ddd, J=19.5, 10.4, 2.4 Hz, 1 H), 1.74 (m, 1 H), 1.65 (s, 3 H), 1.61 (m, 1 H), 1.56 (m, 1H).

Workup

  1. washwashed with water
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe resulting residue was purified by column chromatography on silica gel
  5. washeluting with 10-30% ethyl acetate-hexanes

Sources & evidence

ORD record
ord-5b11338257ed455380af1a4e0e936950
Source dataset
uspto-grants-2013_08
Patent number
US08507559B2

Reaction notes

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