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

HRID 532867노트

반응식

HRID 532867 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-7018f154a8044e1e921d014b33ab1e58
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08853203B2

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