Cesium carbonate → Methyl 3-(2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoate

HRID 219408

Reaction equation

HRID 219408 reaction equation
[C:1](=O)([O-])[O-].[Cs+].[Cs+].Br[C:8]1[CH:9]=[C:10]2[CH:16]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[O:14][C:11]2=[N:12][CH:13]=1.[CH3:24][C:25]1[CH:33]=[CH:32][C:28]([C:29]([OH:31])=[O:30])=[CH:27][C:26]=1B1OC(C)(C)C(C)(C)O1.[Si](C=[N+]=[N-])(C)(C)C>O1CCOCC1.O.CCOC(C)=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>[F:23][C:20]1[CH:21]=[CH:22][C:17]([C:15]2[O:14][C:11]3=[N:12][CH:13]=[C:8]([C:26]4[CH:27]=[C:28]([CH:32]=[CH:33][C:25]=4[CH3:24])[C:29]([O:31][CH3:1])=[O:30])[CH:9]=[C:10]3[CH:16]=2)=[CH:18][CH:19]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 167693TrimethylsilyldiazomethaneHCID 160860864-Methyl-3-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acidHCID 592337145-Bromo-2-(4-fluorophenyl)furo[2,3-b]pyridine

Product 1

HCID 67217293Methyl 3-(2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoateYield 100%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Cesium carbonate (379 mg, 1.164 mmol) was added to a stirring solution of 5-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridine (200 mg, 0.685 mmol), 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (269 mg, 1.027 mmol), Pd(Ph3P)4 (158 mg, 0.137 mmol) in 1,4-dioxane (5.7 mL) and Water (1.1 mL). It was heated to 90° C. overnight. The mixture was diluted with EtOAc and washed with 1M HCl, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and diluted with MeOH/DCM and treated with TMS-diazomethane (685 μL, 1.37 mmol, 2M in ether). The mixture was allowed to stir for 1 hour. The reaction was concentrated and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm) to give the expected product methyl 3-(2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoate (247 mg, 0.685 mmol, quant) by LCMS and NMR. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.28 (1H, d, J=2.26 Hz), 8.16 (1H, d, J=2.01 Hz), 8.01-8.10 (2H, m), 7.93 (1H, dd, J=7.91, 1.88 Hz), 7.85 (1H, d, J=1.76 Hz), 7.49-7.57 (2H, m), 736-7.44 (2H, m), 3.86 (3H, s), 2.34 (3H, s). LC-MS retention time: 2.55 min; m/z (MH+): 362. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. washwashed with 1M HCl
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additiondiluted with MeOH/DCM
  6. concentrationThe reaction was concentrated
  7. customwas purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm)

Sources & evidence

ORD record
ord-9c4daaf36cee4cc29be47bfb2d6b95e2
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Linked notes

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