Iodine → (2S)-2-[4-(iodomethyl)-2-oxo-1-pyrrolidinyl]butanamide

HRID 453255ノート

反応式

HRID 453255 の反応式
O[CH2:2][CH:3]1[CH2:7][N:6]([C@@H:8]([CH2:12][CH3:13])[C:9]([NH2:11])=[O:10])[C:5](=[O:14])[CH2:4]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[I:34]I>C(#N)C>[I:34][CH2:2][CH:3]1[CH2:7][N:6]([C@@H:8]([CH2:12][CH3:13])[C:9]([NH2:11])=[O:10])[C:5](=[O:14])[CH2:4]1

参加物

5

反応物 3

HCID 807IodineHCID 11776TriphenylphosphineHCID 60105803(2S)-2-[4-(hydroxymethyl)2-oxo-1-pyrrolidinyl]butanamide

生成物 1

HCID 9922693(2S)-2-[4-(iodomethyl)-2-oxo-1-pyrrolidinyl]butanamide

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

In a 10 l 3 necked vessel, fitted with mechanical stirrer and reflux condenser under inert atmosphere, 400 g (2 mole, 1 eq) of (2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]butanamide 6 are dissolved in 3 l of acetonitrile. 629 g (2.4 moles, 1.2 eq) of triphenylphosphine are added, followed by 608 g (2.4 moles, 1.2 eq) of iodine in three portions over 5 min. The mixture is heated up to 60° C. in 30 min, and stirred at that temperature for 5 hours. After cooling down, the mixture is concentrated to dryness, the residue suspended in a solution of 750 g of Na2S2O3 in 10 l of water and stirred at 50° C. for 4 hours. The precipitate is filtered off and washed with 3×1 l of water. The combined aqueous phases are treated with 1 kg of NaCl, and extracted with 6×1 l of CH2Cl2. The combined organic phases are dried over MgSO4, filtered and concentrated to dryness to give 482 g of crude 10. It is crystallised from toluene. Several crops are recrystallised together from ethyl acetate to give 425 g of pure 10, 68%.

後処理

  1. temperatureAfter cooling down
  2. concentrationthe mixture is concentrated to dryness
  3. stirringstirred at 50° C. for 4 hours
  4. filtrationThe precipitate is filtered off
  5. washwashed with 3×1 l of water
  6. additionThe combined aqueous phases are treated with 1 kg of NaCl
  7. extractionextracted with 6×1 l of CH2Cl2
  8. dry with materialThe combined organic phases are dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customto give 482 g of crude 10
  12. customIt is crystallised from toluene
  13. customSeveral crops are recrystallised together from ethyl acetate
  14. customto give 425 g of pure 10, 68%

出典と根拠

ORDレコード
ord-e7bfb12a06424d79ad0d4881139efa4c
出典データセット
uspto-grants-2013_07
特許番号
US08492416B2

反応ノート

読み込み中…