Sodium Carbonate → 5-(2-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl)thiazol-5-yl)-2-fluorobenzonitrile

HRID 1891494Notes

Reaction equation

HRID 1891494 reaction equation
Br[C:2]1[S:3][C:4]([C:7]2[CH:8]=[CH:9][C:10]([F:15])=[C:11]([CH:14]=2)[C:12]#[N:13])=[CH:5][N:6]=1.[C:16]([Si:20]([CH3:41])([CH3:40])[O:21][CH:22]1[C:30]2[C:25](=[C:26](B3OC(C)(C)C(C)(C)O3)[CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23]1)([CH3:19])([CH3:18])[CH3:17].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.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>[Si:20]([O:21][CH:22]1[C:30]2[C:25](=[C:26]([C:2]3[S:3][C:4]([C:7]4[CH:8]=[CH:9][C:10]([F:15])=[C:11]([CH:14]=4)[C:12]#[N:13])=[CH:5][N:6]=3)[CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23]1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:41])[CH3:40]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 58354997tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)oxy)silaneHCID 583673815-(2-Bromothiazol-5-yl)-2-fluorobenzonitrile

Product 1

HCID 583671915-(2-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl)thiazol-5-yl)-2-fluorobenzonitrileYield 32%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Prepared using General Procedure 1. To 5-(2-bromothiazol-5-yl)-2-fluorobenzonitrile THZ INT-4 (0.100 g, 0.35 mmol), tert-butyldimethyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yloxy) silane IND INT-8 (0.143 g, 0.38 mmol) and sodium carbonate (0.112 g, 1.1 mmol) in dioxane (1.8 mL) and H2O (0.2 mL) was added tetrakis(triphenylphosphine)palladium (0.041 g, 0.035 mmol). The solution was degassed with N2 and the reaction mixture heated at 85° C. for 6 h. Upon cooling, the reaction mixture was diluted with brine and washed with DCM (3×100 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by chromatography (30% EA/Hexanes) to produce 0.05 g (32%) of 5-(2-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl)thiazol-5-yl)-2-fluorobenzo-nitrile as a white solid. LCMS-ESI (m/z) calculated for C25H27FN2OSSi: 450.6; found 451.1 [M+H] +, tR=4.84 min (Method 3).

Workup

  1. customPrepared
  2. customThe solution was degassed with N2
  3. temperatureUpon cooling
  4. additionthe reaction mixture was diluted with brine
  5. washwashed with DCM (3×100 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by chromatography (30% EA/Hexanes)

Sources & evidence

ORD record
ord-f07da828140641afafa7705c4d63e5b5
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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