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Dichloromethane → 1-(3-Fluoro-5-(6-methoxynaphthalen-2-yl)pyridin-4-yl)ethanol

HRID 1897576
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HRID 1897576 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8](B(O)O)[CH:7]=[CH:6]2.Br[C:17]1[CH:18]=[N:19][CH:20]=[C:21]([F:26])[C:22]=1[CH:23]([OH:25])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:26][C:21]1[CH:20]=[N:19][CH:18]=[C:17]([C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[CH:9]=2)[C:22]=1[CH:23]([OH:25])[CH3:24]
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참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 46416926-Methoxy-2-naphthaleneboronic acidHCID 699379091-(3-Bromo-5-Fluoro-pyridin-4-yl)-ethanol

생성물 1

HCID 699373971-(3-Fluoro-5-(6-methoxynaphthalen-2-yl)pyridin-4-yl)ethanol수율 51%

시약·촉매·용매 2

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
HCID 6228Dimethylformamide용매

실험 절차

A mixture of 6-methoxynaphthalen-2-ylboronic acid (333 mg, 1.650 mmol), 1-(3-bromo-5-fluoropyridin-4-yl)ethanol 4a (330 mg, 1.5 mmol), sodium carbonate (2M in water, 1.5 mL, 3.00 mmol), PdCl2(dppf).CH2Cl2 adduct (61.2 mg, 0.075 mmol) in DMF (6 mL) was heated to 100° C. for 2 hrs. The mixture was quenched with sat NaHCO3 and extracted with EtOAc two times, dried over magnesium sulfate, filtered, concentrated. The residue was purified via Biotage (20-60% EtOAc/heptane; SNAP25 column) giving the title compound (227 mg, 51%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.62 (dd, J=6.7, 1.0 Hz, 3H), 3.96 (s, 3H), 4.99 (q, J=6.7 Hz, 1H), 7.19-7.26 (m, 2H), 7.36 (dd, J=8.4, 1.7 Hz, 1H), 7.70 (s, 1H), 7.78 (d, J=8.9 Hz, 1H), 7.83 (d, J=8.5 Hz, 1H), 8.40 (s, 1H), 8.48 (d, J=2.7 Hz, 1H). LC-MS (M+1) 298.0, t=1.49 min.

후처리

  1. customThe mixture was quenched with sat NaHCO3
  2. extractionextracted with EtOAc two times
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified via Biotage (20-60% EtOAc/heptane; SNAP25 column)

출처 및 근거

ORD 기록
ord-5527eace12414eaf8eef5e23bf530026
출처 데이터셋
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08519134B2

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