Sodium Carbonate → 5-(Bromomethyl)-2-(difluoromethoxy)-3-(3-(oxetan-3-yloxy)phenyl)pyridine

HRID 2271466노트

반응식

HRID 2271466 반응식
[F:1][CH:2]([F:18])[O:3][C:4]1[C:9]([C:10]2[CH:11]=[C:12]([OH:16])[CH:13]=[CH:14][CH:15]=2)=[CH:8][C:7]([CH3:17])=[CH:6][N:5]=1.[Br:19]C1C(OC(F)F)=NC=C(CBr)C=1.[OH:32][C:33]1C=C(B(O)O)C=[CH:37][CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+]>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].C(#N)C.O>[Br:19][CH2:17][C:7]1[CH:8]=[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH:38]3[CH2:33][O:32][CH2:37]3)[CH:11]=2)[C:4]([O:3][CH:2]([F:1])[F:18])=[N:5][CH:6]=1

참가 물질

8

반응물 4

HCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 904147933-Bromo-5-(bromomethyl)-2-(difluoromethoxy)pyridine2회HCID 904152023-(2-(Difluoromethoxy)-5-methylpyridin-3-yl)phenol

생성물 1

HCID 904149725-(Bromomethyl)-2-(difluoromethoxy)-3-(3-(oxetan-3-yloxy)phenyl)pyridine수율 91%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6342Acetonitrile용매

반응 조건

온도
100 °C

실험 절차

3-(2-(Difluoromethoxy)-5-methylpyridin-3-yl)phenol. A 20 mL microwave vial was charged with 3-bromo-2-(difluoromethoxy)-5-methylpyridine (intermediate 4, 1.90 g, 7.98 mmol), 3-hydroxyphenylboronic acid (1.32 g, 9.58 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (330 mg, 0.40 mmol), sodium carbonate (2.12 g, 19.96 mmol), water (4.0 mL), and ACN (12 mL). The vial was sealed, purged with nitrogen, and heated under microwave irradiation at 100° C. for 15 min. The reaction mixture was diluted with water and extracted with DCM (3×). The combined organic phase was dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification (FCC, SiO2, 0-40% EtOAc/hexanes) afforded the title compound (1.81 g, 91%) as a colorless waxy solid. [M+H]=252.12.

후처리

  1. customThe vial was sealed
  2. custompurged with nitrogen
  3. additionThe reaction mixture was diluted with water
  4. extractionextracted with DCM (3×)
  5. dry with materialThe combined organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification (FCC, SiO2, 0-40% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-4f6d6a53547945ea9d3b8760c860e17d
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09120770B2

반응 노트

불러오는 중…