Triethylamine → 4-[(2-Methoxyethoxy)methoxy]benzonitrile

HRID 430893Notes

Reaction equation

HRID 430893 reaction equation
NCCC[C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][C:12]=1[O:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH3:19])[C:8]#[N:9].N1C=CC(C2C=CC(C(O)=O)=CC=2)=CC=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(CC)CC>CN(C=O)C.CCOC(C)=O>[CH3:19][O:18][CH2:17][CH2:16][O:15][CH2:14][O:13][C:12]1[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15208114-(Pyridin-4-yl)benzoic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 18351433HCID 18351433, compound

Product 1

HCID 158520284-[(2-Methoxyethoxy)methoxy]benzonitrileYield 60.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
35 °C

Procedure

3-(3-Aminopropyl)-4-(2-methoxyethoxymethoxy)benzonitrile (88 mg, 0.33 mmol) in DMF (0.5 mL) is added to a mixture of 4-pyridin-4-yl benzoic acid (60 mg, 0.3 mmol), TBTU (106 mg, 0.33 mmol), and Et3N (0.043 mL, 0.033 mmol) in DMF (1 mL). The mixture is stirred at 35° C. for 4 hours. The solution is diluted with EtOAc (20 mL), washed with saturated NaHCO3 (3×17 mL) and brine (3×17 mL), dried over MgSO4, filtered and concentrated. The residue is chromatographed (4% MeOH/CH2Cl2) to give 3-[4-(pyridin-4-yl)-benzamido]propyl)-4-(2-methoxyethoxymethoxy)-benzonitrile (0.09 g, 0.20 mmol), contaminated with an unknown byproduct. The crude material (0.08 g, 0.18 mmol) is dissolved in CH2Cl2 (5 mL), treated with MCPBA (57-86%, 92 mg) at 0° C., a room temperature for 2 hours. The residue from aqueous workup and concentration is treated with anhydrous HCl/EtOH followed by ammonolysis as described in Example 307, part D. HPLC purification (10% MeCN/0.1% TFA in H2O to 100% MeCN) gave the title compound (0.007 g, 0.01 mmol). 1H NMR (CD3OD, 300 MHz) δ8.94 (bs, 1H), 8.65 (bs, 1H), 8.40 (m, 3H), 7.90 (m, 6H), 7.64 (d, 1H), 7.57 (dd, 1H), 6.93 (d, 1H), 3.43 (t, 2H), 2.77 (t, 2H), 1.97 (m, 2H). Ion spray MS [M+1]=391, [M+2]2+=196.

Workup

  1. washwashed with saturated NaHCO3 (3×17 mL) and brine (3×17 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is chromatographed (4% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-dd226250785c45e19d53341084d847cd
Source dataset
uspto-grants-2001_11
Patent number
US06323227B1

Reaction notes

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