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

HRID 532867Notes

Reaction equation

HRID 532867 reaction equation
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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-7018f154a8044e1e921d014b33ab1e58
Source dataset
uspto-grants-2014_10
Patent number
US08853203B2

Reaction notes

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