(Dimethyl sulfide)trihydroboron → (-)-2-(Isochroman-1-yl)ethanol

HRID 368844

反応式

HRID 368844 の反応式
B.CSC.[CH:5]1([CH2:15][C:16](O)=[O:17])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7][O:6]1>C1COCC1>[CH:5]1([CH2:15][CH2:16][OH:17])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7][O:6]1

参加物

4

反応物 2

HCID 12423031(Dimethyl sulfide)trihydroboronHCID 133088642-(3,4-dihydro-1H-2-benzopyran-1-yl)acetic acid

生成物 1

HCID 14141298(-)-2-(Isochroman-1-yl)ethanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Borane-methyl sulfide (10.5 ml) in THF is added to an ice-cooled solution of (-)-(isochroman-1-yl)acetic acid (LXI, EXAMPLE 45--Step 3, 7.08 g, 36.8 mmol). After stirring for 20 min at 0°, the ice bath is removed and the solution is stirred at 20-25° for another 1.7 hr. The reaction flask is then placed in an ice-water bath and methanol is added slowly until no further gas evolution occurs. The solvents are then removed under reduced pressure and methanol is again added and removed a second and third time. The residue is partitioned between dichloromethane, aqueous sodium bicarbonate and saline. The organic phase is separated, dried over sodium sulfate and concentrated to give (-)-2-(isochroman-1-yl)ethanol (LXXIX). This material is added to dimethylaminopyridine (0.22 g, 1.8 mmol), diisopropylethylamine (16.0 ml, 92 mmol) and THF (60 ml). The mixture is cooled in an ice-water bath and methanesulfonyl chloride (3.4 ml, 44.2 mmol) is added dropwise over several minutes. After stirring for 55 min at 0°, 4-(piperazin-1-yl)benzamide (IV, EXAMPLE 47 Step 1, 9.06 g, 44.2 mmol) and ethylene glycol (60 ml) are added. The mixture is heated at 80° overnight and then water is added and the resulting solid is collected and washed with water and toluene. After drying, the solid is passed through silica gel using methanol/dichloromethane (4/96) to give (-)-4-[4-[2-(isochroman-1-yl)ethyl]piperazin-1-yl]benzamide, MS (m/z) 365; IR (mineral oil) 1610, 1239, 1643, 1112, 1622 cm-1.

後処理

  1. customthe ice bath is removed
  2. stirringthe solution is stirred at 20-25° for another 1.7 hr
  3. customThe reaction flask is then placed in an ice-water bath
  4. additionmethanol is added slowly until no further gas evolution
  5. customThe solvents are then removed under reduced pressure and methanol
  6. additionis again added
  7. customremoved a second and third time
  8. customThe residue is partitioned between dichloromethane, aqueous sodium bicarbonate and saline
  9. customThe organic phase is separated
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated

出典と根拠

ORDレコード
ord-6562c1f0d24f46d8ba23806f96966d2a
出典データセット
uspto-grants-2000_10
特許番号
US06133446

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