Water → HCID 10957910, compound

HRID 1077570Notes

Reaction equation

HRID 1077570 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([O:13][CH3:14])[CH:12]=1)[C@@H:9]([CH3:15])[NH:8][C@H:7]([CH3:16])[CH2:6]2.[CH2:17](Cl)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])([O-])=O.[K+].[K+].O>C(C(C)=O)C.CCOCC>[CH2:17]([N:8]1[C@H:7]([CH3:16])[CH2:6][C:5]2[C:10](=[C:11]([O:13][CH3:14])[CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[C@H:9]1[CH3:15])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7503Benzyl ChlorideHCID 11430Potassium CarbonateHCID 11096166HCID 11096166, compound

Product 1

HCID 10957910HCID 10957910, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6569Methyl Ethyl KetoneSolvent

Procedure

Into a stirred solution of (1R, 3R)-1,2,3,4-tetrahydro-6,8-dimethoxy-1,3-dimethyl-isoquinoline (114 mg, 0.5 mmol) and benzyl chloride (137 mg, 1.1 mmol) in methyl ethyl ketone was added K2CO3 (320 mg, 2.3 mmol). The resulting mixture was heated to reflux for 24 h, after which time it was cooled down and poured into H2O. Et2O was added and the organic layer was washed with H2O, brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by MPLC (hexanes/EtOAc/Et3N; 9:1:0.3) to yield N-benzyl-(1R, 3R)-1,2,3,4-tetrahydro-6,8-dimethoxy-1,3-dimethyl-isoquinoline (148 mg, 93%) as a colorless oil; 1H NMR (500 MHz, CDCl3): δ7.40-7.20 [m, benzyl ArH], 6.28 [d, J=2.0 Hz, ArH(7)], 6.23 [d, J=2.0 Hz, ArH(5)], 3.66 [q, J=6.5 Hz, ArCHCH3 ], 3.82 [d, J=14.0 Hz, NCHaHbPh], 3.78 [s, O(6)CH3 ], 3.70 [s, O(8)CH3, 3.50 [ddq, J=10.5, 5.0 and 6.5 Hz, CHaHbCHCH3 ], 3.29 [d, J=14.0 Hz, NCHaHbPh], 2.63 [dd, J=17.0 and 10.5 Hz, CHaHbCH], 2.58 [dd, J=17.0 and 5.0 Hz, CHaHbCH], 1.30 [d, J=6.5 Hz, CH3 (1)], and 1.25 [d, J=6.5 Hz, CH3 (3)]; 13C NMR (75 MHz, CDCl3): δ158.5, 158.4, 141.7, 136.8, 128.4 [2C], 128.1 [3C], 126.4, 104.1, 96.4, 55.2, 55.1, 51.4, 49.8, 45.8, 32.6, 20.0, and 19.5; LRMS (EI): m/z 296 (M+ --CH3, 100), and 91 (44); IR (neat NaCl plates): 2965, 1605, and 1148 cm-1 ; Anal. calcd for C20H25NO2 : C, 77.14; H, 8.09. Found: C, 77.30; H, 8.06.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 24 h
  3. temperatureafter which time it was cooled down
  4. washthe organic layer was washed with H2O, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by MPLC (hexanes/EtOAc/Et3N; 9:1:0.3)

Sources & evidence

ORD record
ord-b4f0c7ba96744407b2ee9a74e5fb4fe1
Source dataset
uspto-grants-1996_08
Patent number
US05543523

Reaction notes

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