Iodine → 2-(2,6-Dichloropyridin-4-ylmethyl)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-ol

HRID 2080573ノート

反応式

HRID 2080573 の反応式
[Mg].II.Br[CH2:5][C:6]1[CH:11]=[C:10]([Cl:12])[N:9]=[C:8]([Cl:13])[CH:7]=1.[F:14][C:15]([F:32])([F:31])[C:16](=[O:30])[CH2:17][C:18]([C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=1[O:28][CH3:29])([CH3:20])[CH3:19]>C(OCC)C>[Cl:12][C:10]1[CH:11]=[C:6]([CH2:5][C:16]([OH:30])([CH2:17][C:18]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[O:28][CH3:29])([CH3:20])[CH3:19])[C:15]([F:14])([F:32])[F:31])[CH:7]=[C:8]([Cl:13])[N:9]=1

参加物

6

反応物 4

HCID 807IodineHCID 27818294-(Bromomethyl)-2,6-dichloropyridineHCID 5462224MagnesiumHCID 100849201,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one

生成物 1

HCID 101949432-(2,6-Dichloropyridin-4-ylmethyl)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-ol

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒3 回

実験手順

To a 100 mL dry round bottom flask was added 73 mg (3.0 mmol) of magnesium powder, a couple of I2 crystals, and 5 mL of dry diethyl ether, and the mixture was allowed to stir under argon. 4-Bromomethyl-2,6-dichloropyridine (723 mg, 3.0 mmol) in 10 mL of diethyl ether was added dropwise through a dropping funnel and the resulting mixture was heated to reflux for 1 hour. 1,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one (278 mg, 1.0 mmol) (Example 1) in diethyl ether (5 mL) was carefully added dropwise through a dropping funnel and the mixture was allowed to stir to reflux temperature for 4 hours and then overnight (16 hours) at room temperature. The reaction was quenched with the addition of 3 mL of aqueous NH4Cl solution, and the resulting mixture was extracted with three 30 mL portions of EtOAc, washed with H2O (10 mL) and brine (10 mL), and the organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel using an EtOAc-hexanes gradient. Combined product fractions were concentrated in vacuo to afford the desired product which was further purified by preparative-HPLC using a gradient of 80%-100% (CH3CN-water) in 15 minutes and a flow rate of 20 mL/min to afford 76 mg of the title compound (17.2% yield) as a yellowish liquid.

後処理

  1. customTo a 100 mL dry round bottom flask
  2. temperaturethe resulting mixture was heated
  3. temperatureto reflux for 1 hour
  4. stirringto stir
  5. temperatureto reflux temperature for 4 hours
  6. customovernight (16 hours)
  7. customat room temperature
  8. customThe reaction was quenched with the addition of 3 mL of aqueous NH4Cl solution
  9. extractionthe resulting mixture was extracted with three 30 mL portions of EtOAc
  10. washwashed with H2O (10 mL) and brine (10 mL)
  11. dry with materialthe organic phase was dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash chromatography on silica gel using an EtOAc-hexanes gradient
  15. concentrationCombined product fractions were concentrated in vacuo

出典と根拠

ORDレコード
ord-e0531c7298e544fda404f403d30118b0
出典データセット
uspto-grants-2011_04
特許番号
US07932392B2

反応ノート

読み込み中…