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

HRID 2252994노트

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HRID 2252994 반응식
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

참가 물질

8

반응물 6

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

생성물 1

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

시약·촉매·용매 1

HCID 180Acetone용매

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온도
55 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-26def9c625294bc9aaf8b9689440d86c
출처 데이터셋
uspto-grants-2008_01
특허 번호
US07323466B2

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