1,2-Dimethoxyethane → Methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate

HRID 407211

반응식

HRID 407211 반응식
[C:1]([NH:4][C:5]1[CH:10]=[C:9](Br)[N:8]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[C:6]=1[O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:3])[CH3:2].[Cl:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[C:27]([F:34])[C:26]=1[O:35][CH3:36].[F-].[Cs+].COCCOC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:28]2[CH:29]=[CH:30][C:25]([Cl:24])=[C:26]([O:35][CH3:36])[C:27]=2[F:34])[N:8]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[C:6]=1[O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:3])[CH3:2]

참가 물질

7

반응물 4

HCID 80711,2-DimethoxyethaneHCID 25953Cesium fluorideHCID 441297064-Chloro-2-fluoro-3-methoxyphenylboronic acidHCID 86600141Methyl 4-acetamido-3-(benzyloxy)-6-bromopicolinate

생성물 1

HCID 71150541Methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매2회

반응 조건

온도
100 °C

실험 절차

Methyl 4-acetamido-3-(benzyloxy)-6-bromopicolinate (prepared as in Kong, L. C. C. et al. U.S. Patent Application Publication 2005/0176767; 1.5 g, 4.0 mmol), (4-chloro-2-fluoro-3-methoxyphenyl)boronic acid (1.2 g, 5.9 mmol), bis(triphenylphosphine)-palladium(II) dichloride (PdCl2(PPh3)2; 278 mg, 0.4 mmol), cesium fluoride (CsF; 1.2 g, 7.9 mmol), 1,2-dimethoxyethane (DME; 7 mL), and H2O (7 mL) were combined and heated in a Biotage microwave at 100° C. for 15 min. H2O was added to the reaction mixture, and the product was extracted with EtOAc. The combined organic extracts were washed with satd aq NaCl, dried with sodium sulfate (Na2SO4), filtered and concentrated. Flash chromatography (SiO2; 0-45% EtOAc/cyclohexane gradient) afforded methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate as a yellow solid: mp 115-120° C.; 1H NMR (400 MHz, CDCl3) δ 8.87 (d, J=1.6 Hz, 1H), 7.66 (s, 1H), 7.59 (dd, J=8.5, 7.7 Hz, 1H), 7.45 (s, 5H), 7.24 (dd, J=8.6, 1.7 Hz, 1H), 5.13 (s, 2H), 4.03 (s, 3H), 3.99 (d, J=1.0 Hz, 3H), 1.88 (s, 3H); ESIMS m/z 459 ([M+H]+).

후처리

  1. extractionthe product was extracted with EtOAc
  2. washThe combined organic extracts were washed with satd aq NaCl
  3. dry with materialdried with sodium sulfate (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-e25d925e87b84e21bb3210939bf99a9a
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754229B2

연결된 노트

불러오는 중…