Morpholine → 4-(1-Methyl-3,4-dihydroisoquinolin-5-yl)morpholine

HRID 532867ノート

反応式

HRID 532867 の反応式
I[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]=[C:7]2[CH3:12].[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:12][C:7]1[C:8]2[C:3](=[C:2]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:5][N:6]=1

参加物

7

反応物 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 867113155-Iodo-1-methyl-3,4-dihydroisoquinoline

生成物 1

HCID 867113164-(1-Methyl-3,4-dihydroisoquinolin-5-yl)morpholine収率 44.9%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

実験手順

A flask under Ar was charged with 5-iodo-1-methyl-3,4-dihydroisoquinoline (8.0 g, 29.5 mmol), morpholine (3.1 g, 35.4 mmol) and Cs2CO3 (13.5 g, 41.3 mmol) and a mixture of Pd(OAc)2 (0.33 g, 1.48 mmol) and BINAP (0.92 g, 1.48 mmol) in toluene (150 mL) was added. The reaction was stirred at RT for 5 min and then heated to reflux for 24 h. The reaction was allowed to cool to RT, and then filtered over celite. The filtrate was concentrated in vacuo and the crude product was purified by flash chromatography (SiO2, DCM to DCM/MeOH 9:1) to provide the title compound (3.05 g). UPLC-MS: MS 231.1 (M+H+); UPLC rt 0.40 min.

後処理

  1. additionwas added
  2. temperatureheated
  3. temperatureto reflux for 24 h
  4. temperatureto cool to RT
  5. filtrationfiltered over celite
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe crude product was purified by flash chromatography (SiO2, DCM to DCM/MeOH 9:1)

出典と根拠

ORDレコード
ord-7018f154a8044e1e921d014b33ab1e58
出典データセット
uspto-grants-2014_10
特許番号
US08853203B2

反応ノート

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