Ammonium Chloride → HCID 86644974, compound

HRID 1944231Notes

Reaction equation

HRID 1944231 reaction equation
[CH3:1][CH:2]1[CH2:11][C:10]2[C:5](=[CH:6][C:7]([O:20][CH3:21])=[C:8]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:9]=2)[CH2:4][NH:3]1.CCN(C(C)C)C(C)C.[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][C:34]=1[CH2:35]Cl.[Cl-].[NH4+]>CN(C=O)C.O>[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][C:34]=1[CH2:35][N:3]1[CH:2]([CH3:1])[CH2:11][C:10]2[C:5](=[CH:6][C:7]([O:20][CH3:21])=[C:8]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:9]=2)[CH2:4]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 2911942,5-Dimethoxybenzyl chlorideHCID 68495203HCID 68495203, compound

Product 1

HCID 86644974HCID 86644974, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

3-Methyl-6-benzyloxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline (338 mg, 1.2 mmol) was dissolved in anhydrous DMF (3.6 mL), DIPEA (314 mg, 2.4 mmol) and 2,5-dimethoxybenzyl chloride (279 mg, 1.5 mmol) were added. The mixture was heated to 80° C. for 20 h, cooled to room temperature and poured into water (50 mL) and ammonium chloride (saturated, 2 mL). The mixture was extracted with ethyl acetate (2×50 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). W8 was obtained as sticky orange oil (395 mg, 76%). 1H NMR (270 MHz, CDCl3) δ 1.14 (3H, d, J 6.3, CHCH3), 2.48 (1H, dd, J 16.3, 6.0, one of ArCH2CH), 2.86 (1H, dd, J 16.1, 4.8, one of ArCH2CH), 3.11 (1H, sext, J 6.1, CHCH3), 3.58-3.77 (4H, m, 2×ArCH2N), 3.76 (3H, s, OCH3), 3.77 (3H, s, OCH3), 3.81 (3H, s, OCH3), 5.11 (2H, s, OCH2Ph), 6.50 (1H, s, CH), 6.61 (1H, s, CH), 6.74 (1H, dd, J 8.8, 3.0, CH), 6.80 (1H, d, J 8.8, CH), 7.07 (1H, d, J 2.8, CH), 7.24-7.47 (5H, m, OCH2C6H5). 13C NMR (67.5 MHz, CDCl3): δ 15.5, 34.5, 50.0, 51.4, 52.4, 55.7, 56.0, 56.0, 71.0, 109.9, 111.3, 111.9, 114.4, 116.0, 125.8, 127.0, 127.2, 127.7, 128.4, 128.9, 137.3, 146.5, 147.7, 151.9, 153.6.

Workup

  1. temperaturecooled to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-35254b41e75142a9a662780903b2b688
Source dataset
uspto-grants-2013_03
Patent number
US08394825B2

Reaction notes

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