Ammonium Chloride → 3-Ethyl-6-benzyloxy-7-methoxy-2-(3,4,5-trimethoxybenzyl)tetrahydroisoquinoline

HRID 1944220Notes

Reaction equation

HRID 1944220 reaction equation
[CH2:1]([CH:3]1[CH2:12][C:11]2[C:6](=[CH:7][C:8]([O:21][CH3:22])=[C:9]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:10]=2)[CH2:5][NH:4]1)[CH3:2].CCN(C(C)C)C(C)C.[CH3:32][O:33][C:34]1[CH:35]=[C:36]([CH:39]=[C:40]([O:44][CH3:45])[C:41]=1[O:42][CH3:43])[CH2:37]Cl.[Cl-].[NH4+]>CN(C=O)C.O>[CH2:1]([CH:3]1[CH2:12][CH:11]2[C:6](=[CH:7][C:8]([O:21][CH3:22])=[C:9]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10]2)[CH2:5][N:4]1[CH2:37][C:36]1[CH:39]=[C:40]([O:44][CH3:45])[C:41]([O:42][CH3:43])=[C:34]([O:33][CH3:32])[CH:35]=1)[CH3:2]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 774485-(Chloromethyl)-1,2,3-trimethoxybenzeneHCID 81531DiisopropylethylamineHCID 68493970HCID 68493970, compound

Product 1

HCID 684940673-Ethyl-6-benzyloxy-7-methoxy-2-(3,4,5-trimethoxybenzyl)tetrahydroisoquinoline

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 261 (297 mg, 1.0 mmol) in anhydrous DMF (3.0 mL), DIPEA (264 mg, 2.0 mmol) and 3,4,5-trimethoxybenzyl chloride (238 mg, 1.1 mmol) was heated to 80° C. for 12 h, cooled to room temperature and poured into water (50 mL) and ammonium chloride (saturated, 2 mL). The mixture was extracted with ethyl acetate (2×30 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography using Flashmaster (SiO2: 20 g, hexane 100% to hexane/ethyl acetate 50:50). The title compound was obtained as pale yellow oil (350 mg, 73%). 1H NMR (270 MHz, CDCl3) δ 0.97 (3H, t, J 7.0, CH2CH3), 1.43 (1H, sept, J 7.0, one of CH2CH3), 1.67 (1H, sept, J 7.0, one of CH2CH3), 2.42-2.58 (1H, m, one of ArCH2CH), 2.72-2.95 (2H, m, one of ArCH2CH, CHN), 3.51-3.74 (4H, m, 2×ArCH2N), 3.80 (3H, s, OCH3), 3.83 (6H, s, 2×OCH3), 3.88 (3H, s, OCH3), 5.10 (2H, s, OCH2Ph), 6.45-6.56 (1H, m, CH), 6.56-6.70 (3H, m, 3×CH), 7.24-7.52 (5H, m, OCH2C6H5).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (2×30 mL)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-bb2453c8f4944081811e340002662b5c
Source dataset
uspto-grants-2013_03
Patent number
US08394825B2

Reaction notes

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