Methyl iodide → HCID 59350839, compound

HRID 1644732Notes

Reaction equation

HRID 1644732 reaction equation
[CH:1]([N-]C(C)C)(C)C.[Li+].[CH3:9][O:10][C:11](=[O:36])[CH2:12][C:13]1[CH:22]=[C:21]([C:23](=[O:34])[C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=2)[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([F:35])[CH:19]=2)[CH:14]=1.CI>O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O>[CH3:9][O:10][C:11](=[O:36])[CH:12]([C:13]1[CH:22]=[C:21]([C:23](=[O:34])[C:24]2[CH:25]=[CH:26][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][CH:29]=2)[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([F:35])[CH:19]=2)[CH:14]=1)[CH3:1]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 66775532HCID 66775532, compound

Product 1

HCID 59350839HCID 59350839, compoundYield 56.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-78 °C

Procedure

To in situ generated lithium diisopropylamide (LDA) (0.33 mmol) [from diisopropylamine (0.33 mmol) and n-butyllithium (0.36 mmol)] in tetrahydrofuran (1.5 mL) at −78° C. under nitrogen was added a solution of [6-fluoro-4-(4-methanesulfonyl-benzoyl)-naphthalen-2-yl]-acetic acid methyl ester (0.120 g, 0.30 mmol, prepared in an analogous manner to the precursor of example 2-1 according to Scheme 2) in tetrahydrofuran (1.0 mL) drop-wise. The reaction mixture was stirred for 30 minutes at −78° C. Methyl iodide (0.051 g, 0.36 mmol) in hexamethylphosphoramide (HMPA) (2.4 mL) was then added drop-wise. The resulting mixture was stirred at −78° C. for 20 minutes, then warmed to −30° C. and stirred for an additional 2 hours. The reaction was quenched with an aqueous solution of saturated ammonium chloride (2 mL), and the resulting mixture was extracted with ethyl acetate (3×5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Flash chromatography (silica gel, 100-200 mesh, 20% ethyl acetate in hexane) gave 2-[6-fluoro-4-(4-methanesulfonyl-benzoyl)-naphthalen-2-yl]-propionic acid methyl ester (0.070 g, 56.4%) as an off-white solid. MS cald. for C22H19FO5S [(M+H)+] 415, obsd. 415.

Workup

  1. customat −78° C.
  2. stirringThe resulting mixture was stirred at −78° C. for 20 minutes
  3. temperaturewarmed to −30° C.
  4. stirringstirred for an additional 2 hours
  5. customThe reaction was quenched with an aqueous solution of saturated ammonium chloride (2 mL)
  6. extractionthe resulting mixture was extracted with ethyl acetate (3×5 mL)
  7. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-931db57f538a48afa4c594d0b9ab6641
Source dataset
uspto-grants-2012_02
Patent number
US08124629B2

Reaction notes

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