3-Methoxybenzyl chloride → HCID 68497982, compound

HRID 1944200Notes

Reaction equation

HRID 1944200 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[CH2:15][NH:14][CH:13]([CH3:21])[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27]Cl>CCO>[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27][N:14]1[CH:13]([CH3:21])[CH2:12][C:11]2[C:16](=[CH:17][C:18]([O:19][CH3:20])=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:10]=2)[CH2:15]1

Participants

4

Reactant 2

HCID 699943-Methoxybenzyl chlorideHCID 68495203HCID 68495203, compound

Product 1

HCID 68497982HCID 68497982, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 213 (300 mg, 1.1 mmol), TEA (0.3 ml, 2.1 mmol) and 3-methoxybenzyl chloride (0.18 ml, 1.3 mmol) in EtOH (3 ml) was heated in the microwave at 130° C. for 1.5 h. The reaction mixture was concentrated in vacuo and the crude residue was dissolved in EtOAc (30 ml) and washed with brine (30 ml). The organic layer was dried (MgSO4) and concentrated in vacuo. Purification (flashmaster: 20 g, 100% hex to 100% EtOAc over 25 min) afforded the title compound (357 mg, 84%) as a colourless oil. 1H NMR (270 MHz; CDCl3) 1.12 (3H, d, J=6.4 Hz, CH3CH), 2.47 (1H, dd, J=16.1, 5.7 Hz, CHH), 2.86 (1H, dd, J=16.1, 4.9 Hz, CHH), 3.0-3.11 (1H, m, CH3CH), 3.55 (2H, t, J=13.4 Hz, CH2), 3.76-3.81 (2H, m, CH2), 3.80 (6H, s, 2×OCH3), 5.10 (2H, s, CH2Ph), 6.47 (1H, s, CH), 6.60 (1H, s, CH), 6.79 (1H, ddd, J=8.2, 2.5, 1.0 Hz, CH), 6.94-6.97 (2H, m, 2×CH), 7.15-7.45 (6H, m, 5×CH, phenyl and CH). 13C (67.5 MHz; CDCl3) 15.31 (CH3), 35.03 (CH2), 51.51 (CH2), 52.27 (CH), 55.32 (CH3), 56.11 (CH3), 57.24 (CH2), 71.21 (CH2), 109.95 (CH), 112.48 (CH), 114.36 (CH), 114.56 (CH), 121.32 (CH),125.83 (C), 126.95 (C), 127.37 (CH), 127.82 (CH), 128.59 (CH), 129.30 (CH), 137.47 (C), 141.35 (C), 146.73 (C), 147.91 (C), 159.77 (C). LC/MS (ES+) tr=1.52 min, m/z 404.25 (M++H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe crude residue was dissolved in EtOAc (30 ml)
  3. washwashed with brine (30 ml)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customPurification (flashmaster: 20 g, 100% hex to 100% EtOAc over 25 min)

Sources & evidence

ORD record
ord-203b5508eb814f208ff5af17807bf59f
Source dataset
uspto-grants-2013_03
Patent number
US08394825B2

Reaction notes

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