4-Chlorophenylboronic acid → Ethyl 5-(4-chlorophenyl)thiophene-2-carboxylate

HRID 1009807Notes

Reaction equation

HRID 1009807 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1>CN(C=O)C.C([O-])(O)=O.[Na+].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>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=2)=[CH:15][CH:14]=1

Participants

6

Reactant 2

HCID 742994-Chlorophenylboronic acidHCID 605723Ethyl 5-bromothiophene-2-carboxylate

Product 1

HCID 2823745Ethyl 5-(4-chlorophenyl)thiophene-2-carboxylateYield 93%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 5-bromothiophene-2-carboxylate (1.0 g, 4.25 mmol), 4-chlorophenylboronic acid (0.998 g, 6.38 mmol), 2.0 M aq NaHCO3 (6.38 ml, 12.76 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.492 g, 0.425 mmol) in DMF (40 ml) under nitrogen was stirred at 100° C. under nitrogen in a sealed tube for 18 hours as described in WO 2007/011284. The reaction was then cooled to RT, diluted with saturated aq NaHCO3 (40 ml) and extracted with EtOAc (40 ml). The EtOAc extracts were dried over Na2SO4 and concentrated. The crude product was purified by ISCO chromatography on a silica gel column (120 g) employing a 10 min gradient ranging from hexane to 30% EtOAc to elute ethyl 5-(4-chlorophenyl)thiophene-2-carboxylate (1.05 g, 3.94 mmol, 93% yield) as a white solid. LC MS at t=2.70 min. (m+H=267) PHENOMENEX® 55 C18 4.6×30 mm column/water-MeOH-TFA 90:10:0.1 to 10:90:0.1 gradient over 2 min at 5 mL/min with 1 min hold at the end of the gradient. 1H NMR (400 MHz, CD3OD) 8 ppm 1.39 (t, J=7.18 Hz, 3H), 4.37 (q, J=7.22 Hz, 2H), 7.43-7.51 (m, 3H), 7.71 (d, J=8.56 Hz, 2H), 7.78 (d, J=4.03 Hz, 1H).

Workup

  1. temperatureThe reaction was then cooled to RT
  2. extractionextracted with EtOAc (40 ml)
  3. dry with materialThe EtOAc extracts were dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude product was purified by ISCO chromatography on a silica gel column (120 g)
  6. waitemploying a 10 min

Sources & evidence

ORD record
ord-cbc4b92f105d423dbead87fc365b93ef
Source dataset
uspto-grants-2011_07
Patent number
US07973159B2

Reaction notes

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