Cesium carbonate → Methyl 2-{[3'-fluoro-4'-(formylamino)-1,1'-biphenyl-4-yl]carbonyl}cyclopentanecarboxylate

HRID 9552

반응식

HRID 9552 반응식
[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[NH:9][CH:10]=[O:11].C([O-])(=O)C.[K+].Br[C:18]1[CH:34]=[CH:33][C:21]([C:22]([C@@H:24]2[CH2:28][CH2:27][CH2:26][C@H:25]2[C:29]([O:31][CH3:32])=[O:30])=[O:23])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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:1][C:2]1[CH:7]=[C:6]([C:18]2[CH:19]=[CH:20][C:21]([C:22]([CH:24]3[CH2:28][CH2:27][CH2:26][CH:25]3[C:29]([O:31][CH3:32])=[O:30])=[O:23])=[CH:33][CH:34]=2)[CH:5]=[CH:4][C:3]=1[NH:9][CH:10]=[O:11]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 23549341N-(2-fluoro-4-iodophenyl)formamideHCID 58681296(1R,2R)-Methyl 2-(4-bromobenzoyl)cyclopentanecarboxylate

생성물 1

HCID 21985795Methyl 2-{[3'-fluoro-4'-(formylamino)-1,1'-biphenyl-4-yl]carbonyl}cyclopentanecarboxylate수율 169.4%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

To a suspension of 2-fluoro-4-iodophenylformamide (5.11 g, 19.28 mmol) bis(pinacolato)diboron (4.89 g, 19.28 mmol), potassium acetate (5.67 g, 57.84 mmol), and palladium acetate (129 mg, 0.58 mmol) in N,N-dimethylformamide (125 mL) was bubbled through argon for 30 minutes. The reaction mixture was then heated at 80° C. for 3 h. After the mixture was cooled to rt, methyl (R,R)-2-(4-bromobenzoyl)cyclopentanecarboxylate (2.2 g, 7.35 mmol, 97% ee), tetrakis(triphenylphosphine)palladium(0) (668 mg, 0.58 mmol), and cesium carbonate (9.43 g, 28.92 mmol) were added, and the reaction mixture was then heated at 80° C. for 16 h. The mixture was then cooled to rt, quenched with water, extracted with ethyl acetate, and dried over anhydrous sodium sulfate. Solvent was then removed under reduced pressure and the crude product was purified by flash chromatography (Biotage 75) using 1:1 ethylacetate/hexane to afford methyl 2-{[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentanecarboxylate (4.6 g, 65%). LC-MS ret. time 3.15 min, m/z 342.0 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.52–1.94 (m, 1H), 1.92–2.07 (m, 1H), 2.10–2.21 (m, 1H), 3.48 (m, 1H), 3.55 (s, 3H), 4.12 (q, 1H), 7.59 (dd, 1H), 7.62 (dd, 1H), 7.87 (d, 2H), 8.09 (d, 2H), 8.25 (t, 1H), 8.34 (s, 1H), 10.62 (s, 1H).

후처리

  1. customwas bubbled through argon for 30 minutes
  2. temperatureAfter the mixture was cooled to rt
  3. temperaturethe reaction mixture was then heated at 80° C. for 16 h
  4. temperatureThe mixture was then cooled to rt
  5. customquenched with water
  6. extractionextracted with ethyl acetate
  7. dry with materialdried over anhydrous sodium sulfate
  8. customSolvent was then removed under reduced pressure
  9. customthe crude product was purified by flash chromatography (Biotage 75)

출처 및 근거

ORD 기록
ord-4206c7f805fd4769a8114cbbd699fa8a
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091228B2

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