2,4-Dimethoxybenzylamine → HCID 68503880, compound

HRID 1715323Notes

Reaction equation

HRID 1715323 reaction equation
[CH3:1][C:2]1([CH3:21])[CH2:6][O:5][C:4](=[O:7])[CH:3]1[O:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([C:17]([F:20])([F:19])[F:18])[CH:10]=1.[CH3:22][O:23][C:24]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:25]=1[CH2:26][NH2:27]>CO>[C:13]([C:12]1[CH:15]=[CH:16][C:9]([O:8][CH:3]([C:2]([CH3:1])([CH3:21])[CH2:6][OH:5])[C:4]([NH:27][CH2:26][C:25]2[CH:28]=[CH:29][C:30]([O:32][CH3:33])=[CH:31][C:24]=2[O:23][CH3:22])=[O:7])=[CH:10][C:11]=1[C:17]([F:20])([F:19])[F:18])#[N:14]

Participants

4

Reactant 2

HCID 5972502,4-DimethoxybenzylamineHCID 11695104HCID 11695104, compound

Product 1

HCID 68503880HCID 68503880, compoundYield 84.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension comprised of (±)-4-(4,4-dimethyl-2-oxo-tetrahydro-furan-3-yloxy)-2-trifluoromethyl-benzonitrile (81.55 g; 272.5 mmol), 2,4-dimethoxybenzylamine (50.40 g; 295.4 mmol), and methanol (300 mL) was stirred at ambient temperature under a nitrogen atmosphere overnight. The suspension became a clear solution. The reaction mixture was concentrated in vacuo to afford a cloudy orange oil (145 g.) The oil was triturated with diethyl ether (500 mL) over a steam bath to gentle boiling. The flask was removed from the steam bath as a solid began to slowly form. The oil was scratched with a spatula which accelerated solid formation and the solids were collected by vacuum filtration to afford 107.25 g of an off-white amorphous solid. The mother liquor was concentrated in vacuo to give 28.35 g of a crude red-brown oil. This oil was purified by flash silica column chromatography (Isco Fraction Collector with Biotage 65i 330 g silica cartridge.) Elution with a gradient (98:2 v/v hexanes-ethyl acetate to 100% ethyl acetate over 1 hour, 12 minutes, 18×150 mm tubes, each filled to 27 mL mark in 30 seconds) afforded 20 g of a light-yellow solid. The material was recrystallized from diethyl ether to afford 9.659 g of a white crystalline solid; 1H-NMR (400 MHz; CDCl3) δ 7.61 (d, 1H, J=8.8 Hz), 7.24 (d, 1H, J=2.5 Hz), 7.07 (d, 1H, J=8.2 Hz), 6.94 (dd, 1H, J=8.8, 2.5 Hz), 6.58 (t, 1 H, J=5.6 Hz), 6.37 (dd, 1H, J=8.4, 2.5 Hz), 6.28 (d, 1H, J=2.4 Hz), 4.52 (s, 1H), 4.37-4.25 (m, 2H), 3.78 (s, 3H), 3.58 (s, 3H), 3.50 (d, 1H, J=11.7 Hz), 3.42 (d, 1H, J=11.7 Hz), 1.09 (s, 3H), 0.97 (s, 3H); 19F-NMR (376 MHz; CDCl3) δ −62.70 (s, 3F); MS (APCl+) 467.3 (M+1,100); (APCl−) 465.2 (M−1, 14), 186.0 (100).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto afford a cloudy orange oil (145 g.) The oil
  3. customwas triturated with diethyl ether (500 mL) over a steam bath to gentle boiling
  4. customThe flask was removed from the steam bath as a solid
  5. customto slowly form
  6. filtrationthe solids were collected by vacuum filtration

Sources & evidence

ORD record
ord-919b3c9b7c264857ae31488c1e32c41b
Source dataset
uspto-grants-2010_09
Patent number
US07799823B2

Reaction notes

Loading…