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

HRID 578825ノート

反応式

HRID 578825 の反応式
[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

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 904147933-Bromo-5-(bromomethyl)-2-(difluoromethoxy)pyridine2 回HCID 904152023-(2-(Difluoromethoxy)-5-methylpyridin-3-yl)phenol

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-3f0f4f4bcfb148058c43b0e669d8608f
出典データセット
uspto-grants-2015_05
特許番号
US09040692B2

反応ノート

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