تفاعل #72378

ord-10ec0c64b09d4d37ab9ec61c3cfbad64

معادلة التفاعل

c1ccc(P(CCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
1,3-bis(diphenylphosphino)propane
Cc1ccc(C(=O)OC(C)(C)C)cc1-c1cnc2oc(-c3ccc(F)cc3)c(Br)c2c1
tert-butyl 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoate
COC(=O)c1c(-c2ccc(F)cc2)oc2ncc(-c3cc(C(=O)OC(C)(C)C)ccc3C)cc12
methyl 5-(5-(tert-butoxycarbonyl)-2-methylphenyl)-2-(4-fluorophenyl)furo[2,3-b]pyridine-3-carboxylate
المردود 190.8%

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    workup.ADDITIONwas then charged with 300 psi CO (g)
  2. 2
    ترشيحfiltered through a pad of celite
  3. 3
    غسيلThe filtrate was washed with sat. aq. NaHCO3, and brine
  4. 4
    تجفيفThe organic phase was dried over Na2SO4
  5. 5
    ترشيحfiltered
  6. 6
    تركيزconcentrated

الإجراء التجريبي

1,3-bis(diphenylphosphino)propane (119 mg, 0.287 mmol) was added to a stirring solution of palladium(II) acetate (32 mg, 0.144 mmol) and tert-butyl 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoate (231 mg, 0.479 mmol) in MeOH (1.6 mL) and DMSO (3 mL) at 80° C. in a PARR bomb which was then charged with 300 psi CO (g) and allowed to stir overnight. The mixture was diluted with EtOAc and filtered through a pad of celite. The filtrate was washed with sat. aq. NaHCO3, and brine. The organic phase was dried over Na2SO4, filtered and concentrated to give the expected product methyl 5-(5-(tert-butoxycarbonyl)-2-methylphenyl)-2-(4-fluorophenyl)furo[2,3-b]pyridine-3-carboxylate (211 mg, 0.457 mmol, 95% yield) crude by LCMS which was used directly in the next step. LC-MS retention time: 2.32 min; m/z (MH+): 462. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 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 5% MeOH/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% MeOH/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08536338B2uspto-grants-2013_09