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2-Fluoro-3-methoxyphenylboronic acid → 1-(2,6-Difluorobenzyl)-2,6-dimethyl-3-(2-fluoro-3-methoxyphenyl)-5-ethoxycarbonyl-4-pyridone

HRID 495522
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HRID 495522 반응식
[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][N:5]1[C:10]([CH3:11])=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:8](=[O:17])[C:7](Br)=[C:6]1[CH3:19].[F:25][C:26]1[C:31]([O:32][CH3:33])=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O.[OH-].[Ba+2].[OH-]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C=CC=CC=1.C(O)C.COCCOC>[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][N:5]1[C:10]([CH3:11])=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:8](=[O:17])[C:7]([C:27]2[CH:28]=[CH:29][CH:30]=[C:31]([O:32][CH3:33])[C:26]=2[F:25])=[C:6]1[CH3:19]
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참가 물질

6

반응물 3

HCID 49857442-Fluoro-3-methoxyphenylboronic acidHCID 6093286Barium hydroxideHCID 223272271-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-ethoxycarbonyl-4-pyridone

생성물 1

HCID 223272391-(2,6-Difluorobenzyl)-2,6-dimethyl-3-(2-fluoro-3-methoxyphenyl)-5-ethoxycarbonyl-4-pyridone

시약·촉매·용매 2

HCID 11979704
Tetrakis(triphenylphosphine)palladium
촉매
HCID 86588578Benzene ethanol 1,2-dimethoxyethane용매

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온도
90 °C

실험 절차

1-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-ethoxycarbonyl-4-pyridone (1.5 g, 3.7 mmol) was evacuated in a pressure vessel with 2-fluoro-3-methoxyphenyl boronic acid (764 mg, 4.5 mmol) and tetrakis(triphenylphosphine) palladium (0) (428 mg, 370 μmol). A mixture of benzene/ethanol/1,2-dimethoxyethane (74 ml in a 10/1/11 ratio) and barium hydroxide (saturated aqueous, about 0.5M) was then added under vacuum, the vessel sealed under N2, and the reaction stirred at 90° C. for twelve hours, protected from light. The organic layer was concentrated and purified using flash silica chromatography (EtOAc/hexanes-1/4 to MeOH/CH2Cl2-2/98), with the product eluting as the third spot. The product was dried as an amber oil (1.12 g, 2.5 mmol, 68%). 1H NMR (CDCl3, 300 MHz) δ 6.80-7.80 (m, 6H), 5.29 (s, 2H), 4.37-4.33 (m, 2H), 3.87 (s, 3H), 3.38 (s, 3H), 2.26 (s, 3H), 1.35 (t, 3H); LCMS=446 (MH+).

후처리

  1. additionwas then added under vacuum
  2. customthe vessel sealed under N2
  3. concentrationThe organic layer was concentrated
  4. custompurified
  5. washwith the product eluting as the third spot

출처 및 근거

ORD 기록
ord-cb613d474c1244ab84f3549f06c19176
출처 데이터셋
uspto-grants-2005_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06939883B2

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