Trimethylsilyldiazomethane → [4-(5-tert-Butyl-3-ethynyl-4-isopropoxy-2-methyl-phenylethynyl)-phenyl]-acetic acid methyl ester

HRID 1765860Notes

Reaction equation

HRID 1765860 reaction equation
C[Si](C=[N+]=[N-])(C)C.[CH2:8]([Li])CCC.[CH3:13][O:14][C:15](=[O:42])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]#[C:24][C:25]2[CH:30]=[C:29]([C:31]([CH3:34])([CH3:33])[CH3:32])[C:28]([O:35][CH:36]([CH3:38])[CH3:37])=[C:27]([CH:39]=O)[C:26]=2[CH3:41])=[CH:19][CH:18]=1>O1CCCC1>[CH3:13][O:14][C:15](=[O:42])[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]#[C:24][C:25]2[CH:30]=[C:29]([C:31]([CH3:32])([CH3:34])[CH3:33])[C:28]([O:35][CH:36]([CH3:38])[CH3:37])=[C:27]([C:39]#[CH:8])[C:26]=2[CH3:41])=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 167693TrimethylsilyldiazomethaneHCID 60029385HCID 60029385, compound2×HCID 178418339Butyllithium

Product 1

HCID 86600193[4-(5-tert-Butyl-3-ethynyl-4-isopropoxy-2-methyl-phenylethynyl)-phenyl]-acetic acid methyl esterYield 11.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Anhydrous tetrahydrofuran (3 mL) was added to a 2M solution of trimethylsilyl diazomethane in hexanes (0.37 mL, 0.74 mmol) and the resulting reaction mixture was cooled to −78° C. A solution of 1.6M n-butyl lithium in hexanes (0.5 mL, 0.8 mmol) was added followed, after 30 minutes, by a solution of [4-(5-tert-butyl-3-formyl-4-isopropoxy-2-methyl-phenylethynyl)-phenyl]-acetic acid methyl ester (Intermediate 144, 0.2 g, 0.49 mmol) in anhydrous tetrahydrofuran and the resulting reaction mixture was stirred at −78° C. for 1 h and at 0° C. for 40 minutes. The reaction mixture was then quenched with saturated aqueous ammonium chloride solution and extracted with diethyl ether. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a residue that was subjected to flash column chromatography over silica gel (230–400 mesh) using 2.5–4% ethyl acetate in hexane as the eluent followed by preparative normal phase HPLC using 5% ethyl acetate in hexane as the mobile phase to afford the title product as a colorless oil (0.023 g, 11.6%).

Workup

  1. customthe resulting reaction mixture
  2. customthe resulting reaction mixture
  3. customThe reaction mixture was then quenched with saturated aqueous ammonium chloride solution
  4. extractionextracted with diethyl ether
  5. washThe organic phase was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo to a residue that

Sources & evidence

ORD record
ord-0a853cf6d45f470da3e2d71178ef2eac
Source dataset
uspto-grants-2007_06
Patent number
US07226951B2

Reaction notes

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