Acetaldehyde → 1-(3,5-Dichloropyridin-4-yl)ethanol

HRID 41508

反応式

HRID 41508 の反応式
C(NC(C)C)(C)C.C([Li])CCC.[Cl:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([Cl:20])[CH:19]=1.[CH:21](=[O:23])[CH3:22]>O1CCCC1.COC(C)(C)C.[Cl-].[NH4+].O>[Cl:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([Cl:20])[C:19]=1[CH:21]([OH:23])[CH3:22]

参加物

9

反応物 4

HCID 177AcetaldehydeHCID 7912DiisopropylamineHCID 171533,5-DichloropyridineHCID 178418339Butyllithium

生成物 1

HCID 666447221-(3,5-Dichloropyridin-4-yl)ethanol

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 15413tert-Butyl methyl ether溶媒HCID 25517Ammonium Chloride溶媒2 回

反応条件

温度
-78 °C

実験手順

To a 3-neck 12 L round bottom flask add tetrahydrofuran (THF, 3 L) and diisopropylamine (DIPA, 315 mL, 2.24 mol) and cool to −78° C. Add slowly n-butyllithium (1.6 M in hexanes, 1400 mL, 2.24 mol). After the addition is complete and the temperature has settled at −78° C. slowly add a solution of 3,5-dichloropyridine (296.7 g, 2.00 mol) which immediately forms a yellow solution that changes to a rust colored suspension. After the addition is complete and the temperature has settled at −78° C. slowly add acetaldehyde (230 mL, 4.05 mol) in THF (600 mL). Continue stirring at −78° C. After 3 hours, remove the dry ice bath and begin quenching the reaction by the dropwise addition of saturated aqueous ammonium chloride (1 L). Allow the reaction to warm to room temperature (RT) overnight with stirring. Dilute the mixture with methyl-tert-butylether (MTBE, 2 L), saturated aqueous ammonium chloride (1 L) and water (2 L). Partition and wash organics with saturated aqueous sodium chloride (brine). Extract the aqueous phase with MTBE (1.5 L). Combine the organic layers, dry over sodium sulfate, filter and concentrate in vacuo. Purify the residue by silica gel chromatography [25% ethylacetate (EA) in hexanes] to give the title compound as a red oil. Yield: 352 g (90%). MS (ES) m/z 192 [M+1]+.

後処理

  1. additionAfter the addition
  2. customhas settled at −78° C.
  3. additionAfter the addition
  4. customhas settled at −78° C.
  5. customremove the dry ice bath
  6. custombegin quenching
  7. customthe reaction
  8. customthe reaction
  9. temperatureto warm to room temperature (RT) overnight
  10. stirringwith stirring
  11. customPartition
  12. washwash organics with saturated aqueous sodium chloride (brine)
  13. extractionExtract the aqueous phase with MTBE (1.5 L)
  14. dry with materialCombine the organic layers, dry over sodium sulfate
  15. filtrationfilter
  16. concentrationconcentrate in vacuo
  17. customPurify the residue by silica gel chromatography [25% ethylacetate (EA) in hexanes]

出典と根拠

ORDレコード
ord-db0e15b92da54061934686511d939227
出典データセット
uspto-grants-2013_09
特許番号
US08530665B2

関連ノート

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