4-Bromotoluene → HCID 22323723, compound

HRID 324229Notes

Reaction equation

HRID 324229 reaction equation
BrC1C=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.[C:9]([Li])([CH3:12])([CH3:11])[CH3:10].CC1(C)C2[C:18](=[CH:19][C:20]([C:24]#[C:25][C:26]3[CH:36]=[CH:35][C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][CH:27]=3)=CC=2)[C:17](OS(C(F)(F)F)(=O)=O)=C1.[CH3:46][CH2:47][CH2:48][CH2:49][CH3:50]>C1COCC1.[Cl-].[Cl-].[Zn+2].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>[CH3:10][C:9]1([CH3:12])[C:17]2[C:47](=[CH:46][C:20]([C:24]#[C:25][C:26]3[CH:27]=[CH:28][C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:35][CH:36]=3)=[CH:19][CH:18]=2)[C:48]([C:49]2[CH:3]=[CH:4][C:5]([CH3:8])=[CH:6][CH:50]=2)=[CH:11]1

Participants

8

Reactant 4

HCID 78054-BromotolueneHCID 8003PentaneHCID 22323740HCID 22323740, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 22323723HCID 22323723, compound

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 32.0 mg (0.187 mmol) of 4- bromotoluene in 1.0 ml THF was cooled to −78° C. and 24.0 mg of t-butyllithium (0.375 mmol, 0.22 ml of a 1.7 M solution in pentane) was slowly added. The yellow solution was stirred for 30 minutes at which time 29.8 mg (0.219 mmol) of ZnCl2 was added as a solution in 1.0 ml THF. The resulting solution was warmed to room temperature and after 30 minutes added to a second flask containing 29.0 mg (0.062 mmol) of ethyl 4-(2- (1,1-dimethyl-3-(trifluoromethylsulfonyl)oxy-5-indenyl) ethynyl]benzoate (Compound FF) and 2.9 mg (0.003 mmol) of tetrakis(triphenylphosphine)palladium (0) in 1.0 ml THF. The resulting solution was warmed to 50° C. for 1 hour and then stirred at room temperature for 4 hours. The reaction was quenched by the addition of saturated aqueous NH4Cl, and then extracted with Et2O. The combined organic layers were washed with water, saturated aqueous NaCl, and dried over MgSO4 before being concentrated under reduced pressure. The title compound was isolated as a colorless oil by column chromatography (10% Et2O / hexanes). 1H NMR (300 MHz, CDCl3): δ 8.03 (2H, d, J=8.5 Hz), 7.66 (1H, s), 7.58 (2H, d, J 8.5 Hz), 7.50 (2H, d, J=8.0 Hz), 7.46 (1H, d, J=7.9 Hz), 7.38 (1H, d, J=7.7 Hz), 7.28 (2H, d, J=9 Hz), 6.43 (1H, s), 4.40 (2H, q, J=7.2 Hz), 2.43 (3H, s), 1.41 (3H, t; +6H, s).

Workup

  1. additionadded to a second flask
  2. temperatureThe resulting solution was warmed to 50° C. for 1 hour
  3. customThe reaction was quenched by the addition of saturated aqueous NH4Cl
  4. extractionextracted with Et2O
  5. washThe combined organic layers were washed with water, saturated aqueous NaCl
  6. dry with materialdried over MgSO4
  7. concentrationbefore being concentrated under reduced pressure

Sources & evidence

ORD record
ord-ad3f7999920a47c08b4b9a68ae08752b
Source dataset
uspto-grants-2001_04
Patent number
US06218128B1

Reaction notes

Loading…