Dichloromethane → HCID 66731831, 화합물

HRID 1963180노트

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HRID 1963180 반응식
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[K+].[K+].[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B2OC(C)(C)C(C)(C)O2)=[CH:21][C:20]=1[F:34].C(Cl)Cl>CO.Cl[Pd]Cl.O>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[CH:21][C:20]=1[F:34]

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 222401464-Chloro-3-fluorophenylboronic acid pinacol ester

생성물 1

HCID 66731831HCID 66731831, 화합물수율 79.3%

시약·촉매·용매 3

HCID 24290Palladium Chloride촉매HCID 887Methanol용매HCID 962Water용매

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온도
100 °C

실험 절차

Methyl 2-chloroisonicotinate (1.2 g, 6.99 mmol), potassium carbonate (0.580 g, 4.20 mmol) and PdCl2 (dppf) (0.122 g, 0.17 mmol) were combined in a microwave vial. 2-(4-Chloro-3-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.1 g, 8.19 mmol) dissolved in MeOH (15 mL) was added. The reaction mixture was heated in a single node microwave reactor at 100° C. for 15 min. DCM (125 mL) and water (125 mL) were added, shaken and the phases separated. The aqueous phase was extracted with DCM (125 mL). The combined organic phases were washed with brine (250 mL), dried with a phase separator and evaporated in vacuo. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 100 g column. A gradient of 10% EtOAc in heptane over 3 CV and then 10 to 50% EtOAc in heptane over 12 CV was used as mobile phase. The product was collected using the wavelength 253 nm. Methyl 2-(4-chloro-3-fluorophenyl)isonicotinate (1.473 g, 79%) was isolated as a white solid. 1H NMR (400 MHz, cdcl3) δ 4.00 (s, 3H), 7.48-7.54 (m, 1H), 7.76-7.83 (m, 2H), 7.88-7.94 (m, 1H), 8.24-8.27 (m, 1H), 8.83 (dd, 1H).

후처리

  1. additionwas added
  2. customthe phases separated
  3. extractionThe aqueous phase was extracted with DCM (125 mL)
  4. washThe combined organic phases were washed with brine (250 mL)
  5. customdried with a phase separator
  6. customevaporated in vacuo
  7. customThe residue was purified by automated flash chromatography on a Biotage® KP-SIL 100 g column
  8. customThe product was collected

출처 및 근거

ORD 기록
ord-1bd3ae02c224450b95ff3c2cddce821b
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415378B2

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