Toluene → HCID 67486711, compound

HRID 2371297Notes

Reaction equation

HRID 2371297 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:11]1(C)C=CC=CC=1.[CH3:18][O:19][C:20](=[O:49])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH:28]([C:39]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:40])[C:29]2[CH:34]=[CH:33][C:32]([C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:31][CH:30]=2)=[CH:23][CH:22]=1.IC>C1COCC1.C(OCC)(=O)C>[CH3:18][O:19][C:20](=[O:49])[C:21]1[CH:22]=[CH:23][C:24]([CH2:27][C:28]([C:39]([O:41][CH2:42][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)=[O:40])([C:29]2[CH:34]=[CH:33][C:32]([C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:31][CH:30]=2)[CH3:11])=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 67486274HCID 67486274, compound

Product 1

HCID 67486711HCID 67486711, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

A solution of LiHMDS in toluene (1.0M, 1.6 mL, 1.6 mmol) was cooled in a dry-ice acetone bath (−78° C.) and diluted with 3 mL of THF. A solution of 4-[2-Benzyloxycarbonyl-2-(4-tert-butyl-phenyl)-ethyl]-benzoic acid methyl ester (675 mg, prepared as described in Bioorg. Med. Chem Lett. 2004, 14, 2047-2050) in 5 mL of THF was added via cannula. The mixture was stirred at the same temperature 30 min. It was then transferred to an acetone/ice bath, where it was warmed to ˜10° C. over a 1.5 h period. The mixture was cooled back to −78° C. and iodomethane (0.11 mL) was added via syringe. The mixture was then stirred for a 2 h period while allowing it to warm up to room temperature (approximately 2 h). The mixture was poured over a mixture of ethyl acetate and ice cold aqueous ammonium chloride. The organic phase was washed with water and saturated aqueous sodium chloride and dried over magnesium sulfate. The residue obtained after removal of the solven was treated with hexanes/ethyl acetate to cause the formation to precipitate the title compound (307 mg, 44%) HNMR (500 MHz, DMSO-d6, selected signals): 5.12 (2H, ABquartet), 3.82 (3H, s), 3.47 (1H, d, J=13.0 Hz), 3.22 (1H, d, J=13.2 Hz), 1.37 (3H, s), 1.28 (9H, s)

Workup

  1. customIt was then transferred to an acetone/ice bath
  2. temperatureThe mixture was cooled back to −78° C.
  3. stirringThe mixture was then stirred for a 2 h period
  4. temperatureto warm up to room temperature (approximately 2 h)
  5. washThe organic phase was washed with water and saturated aqueous sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. customThe residue obtained
  8. customafter removal of the solven
  9. additionwas treated with hexanes/ethyl acetate
  10. customto precipitate the title compound (307 mg, 44%) HNMR (500 MHz, DMSO-d6, selected signals): 5.12 (2H, ABquartet), 3.82 (3H, s), 3.47 (1H, d, J=13.0 Hz), 3.22 (1H, d, J=13.2 Hz), 1.37 (3H, s), 1.28 (9H, s)

Sources & evidence

ORD record
ord-50abdb391bbe4a229c0a737e873328af
Source dataset
uspto-grants-2014_04
Patent number
US08710236B2

Reaction notes

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