Propargyl bromide → (r)-2-(3-Chloro-4-(prop-2-yn-1-yloxy)benzyl)morpholine

HRID 2252994ノート

反応式

HRID 2252994 の反応式
C([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([Cl:22])[CH:16]=2)[CH2:9]1)(OC(C)(C)C)=O.C(=O)([O-])[O-].[K+].[K+].[CH2:29](Br)[C:30]#[CH:31].C1(S)C=CC=CC=1.C(=O)([O-])[O-].C(N(C(C)C)CC)(C)C>CC(C)=O>[Cl:22][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][C:18]=1[O:21][CH2:31][C:30]#[CH:29])[CH2:14][C@H:10]1[O:11][CH2:12][CH2:13][NH:8][CH2:9]1

参加物

8

反応物 6

HCID 7842Propargyl bromideHCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 19660Carbonate IonHCID 81531DiisopropylethylamineHCID 67073025n-Boc-(r)-2-(3-chloro-4-hydroxybenzyl)morpholine

生成物 1

HCID 11608656(r)-2-(3-Chloro-4-(prop-2-yn-1-yloxy)benzyl)morpholine

試薬・触媒・溶媒 1

HCID 180Acetone溶媒

反応条件

温度
55 °C

実験手順

N-BOC-(R)-2-(3-chloro-4-hydroxybenzyl)morpholine, example 7, intermediate (a) (52 mg, 0.16 mmol), was dissolved in acetone (1.5 mL) with potassium carbonate (44 mg, 0.32 mmol) and propargyl bromide (53 uL, 0.47 mmol) added in one portion. The reaction was then heated to 55° C. and shaken at that temperature for 16 hrs. The reaction mixture was filtered, washing with acetone (1 mL×2) and the liquor evaporated under a high flow of nitrogen. The residue was dissolved in tetrahydrofuran: ethanol (1:1, 4 mL) and polymer supported thiophenol (0.43 g, 0.64 mmol), MP-carbonate (0.24 g, 0.64 mmol) and diisopropylethylamine (119 uL, 0.68 mmol) added. The reaction was shaken for 24 hrs, then filtered and concentrated under a high flow of nitrogen. The crude residue was dissolved in TFA (20% v/v solution in dichloromethane, 2.0 mL) and shaken for 3 hrs at room temperature. The reaction mixture was added directly to an SCX-2 column (2 g) and washed with dichloromethane (2 mL×2) and methanol (2 mL×2). The SCX-2 column was then washed with ammonia (2N in methanol, 3×2 mL). Combined ammonia washes were concentrated in vacuo to yield the desired morpholine example 39 as a colorless oil (20 mg).

後処理

  1. additionadded in one portion
  2. filtrationThe reaction mixture was filtered
  3. washwashing with acetone (1 mL×2)
  4. customthe liquor evaporated under a high flow of nitrogen
  5. dissolutionThe residue was dissolved in tetrahydrofuran: ethanol (1:1, 4 mL)
  6. additionadded
  7. stirringThe reaction was shaken for 24 hrs
  8. filtrationfiltered
  9. concentrationconcentrated under a high flow of nitrogen
  10. dissolutionThe crude residue was dissolved in TFA (20% v/v solution in dichloromethane, 2.0 mL)
  11. stirringshaken for 3 hrs at room temperature
  12. additionThe reaction mixture was added directly to an SCX-2 column (2 g)
  13. washwashed with dichloromethane (2 mL×2) and methanol (2 mL×2)
  14. washThe SCX-2 column was then washed with ammonia (2N in methanol, 3×2 mL)
  15. concentrationCombined ammonia washes were concentrated in vacuo

出典と根拠

ORDレコード
ord-26def9c625294bc9aaf8b9689440d86c
出典データセット
uspto-grants-2008_01
特許番号
US07323466B2

反応ノート

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