Thiazole → Ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(2-thiazolyl)-2-naphthalenyl)ethynyl]benzoate

HRID 495912Notes

Reaction equation

HRID 495912 reaction equation
[CH2:1]([Li:5])CCC.[S:6]1[CH:10]=[CH:9][N:8]=[CH:7]1.[CH3:11][C:12]1([CH3:42])[CH2:21][CH:20]=[C:19](C2C=CC(C)=CC=2)[C:18]2[CH:17]=[C:16]([C:29]#[C:30][C:31]3[CH:41]=[CH:40][C:34]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:33][CH:32]=3)[CH:15]=[CH:14][C:13]1=2>C1COCC1.[NH4+].[Cl-].[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Li:5][C:1]1[S:6][CH:10]=[CH:9][N:8]=1.[CH3:42][C:12]1([CH3:11])[CH2:21][CH:20]=[C:19]([C:7]2[S:6][CH:10]=[CH:9][N:8]=2)[C:18]2[CH:17]=[C:16]([C:29]#[C:30][C:31]3[CH:32]=[CH:33][C:34]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:40][CH:41]=3)[CH:15]=[CH:14][C:13]1=2

Participants

9

Reactant 3

HCID 9256ThiazoleHCID 11796412AGN 193109 Ethyl Ester2×HCID 178418339Butyllithium

Product 2

HCID 15430593Ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(2-thiazolyl)-2-naphthalenyl)ethynyl]benzoateHCID 178506781HCID 178506781, compound

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent3×HCID 25517Ammonium ChlorideSolvent

Procedure

A solution of 2-lithiothiazole was prepared by the addition of 41.2 mg (0.42 ml, 0.63 mmol) of n-butyl-lithium (1.5M solution in hexanes) to a cold solution (−78 ° C.) of 53.4 mg (0.63 mmol) of thiazole in 1.0 ml of THF. The solution was stirred at for 30 minutes and then a solution of 113.9 mg (0.84 mmol) of zinc chloride in 1.5 ml of THF was added. The resulting solution was warmed to room temperature, stirred for 30 minutes and then the organozinc was added via cannula to a solution of 200.0 mg. (0.42 mmol) of ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(trifluoromethylsulfonyl)oxy-2-naphthalenyl)ethynyl]benzoate (Compound G) and 12.4 mg (0.01 mmol) of tetrakis(triphenylphosphine)palladium(0) in 1.5 ml of THF. The resulting solution was heated at 50° C. for 45 minutes, cooled to room temperature and diluted with sat aqueous NH4Cl. The mixture was extracted with EtOAc (40 ml) and the combined organic layers were washed with water and brine. The organic phase was dried over Na2SO4 and concentrated in-vacuo to a yellow oil. Purification by column chromatography (silica, 20% EtOAc-hexanes) yielded the title compound as a colorless oil. PMR (CDCl3): δ 1.35 (6H, s), 1.40 (3H, t, J=7.1 Hz), 2.42 (2H, d, J=4.8 Hz), 4.38 (2H, q, J=7.1 Hz), 6.57 (1H, t, J=4.8 Hz), 7.33 (1H, d, J=3.3 Hz), 7.36 (1H, d, J=8.0 Hz), 7.46 (1H, dd, J=1.7, 8.1 Hz), 7.55 (2H, d, J=8.4 Hz), 7.87 (1H, d, J=1.7 Hz), 7.92 (1H, d, J=3.3 Hz), 8.00 (2H, d, J=8.4 Hz).

Workup

  1. stirringstirred for 30 minutes
  2. temperatureThe resulting solution was heated at 50° C. for 45 minutes
  3. temperaturecooled to room temperature
  4. extractionThe mixture was extracted with EtOAc (40 ml)
  5. washthe combined organic layers were washed with water and brine
  6. dry with materialThe organic phase was dried over Na2SO4
  7. concentrationconcentrated in-vacuo to a yellow oil
  8. customPurification by column chromatography (silica, 20% EtOAc-hexanes)

Sources & evidence

ORD record
ord-f1106ac494c74b7980529e6c63fbb900
Source dataset
uspto-grants-2005_09
Patent number
US06942980B1

Reaction notes

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