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

HRID 44097

反応式

HRID 44097 の反応式
[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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

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 (1 H, dd, J=7.91, 1.88 Hz), 7.85 (1H, d, J=1.76 Hz), 7.49-7.57 (2H, m), 7.36-7.44 (2 H, 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.

後処理

  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)

出典と根拠

ORDレコード
ord-57641716b1e64a4582f72ba60d5599cf
出典データセット
uspto-grants-2013_09
特許番号
US08536338B2

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