4-Chloroanisole → 1-(2'-Fluorophenyl)-2-(4'-methoxyphenyl)-1-propanon

HRID 595354Notes

Reaction equation

HRID 595354 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](Cl)=[CH:5][CH:4]=1.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17](=[O:20])[CH2:18][CH3:19].C(O[Na])(C)(C)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.COC1C=CC=C(N(C)C2C=CC=CC=2)C=1P(C1CCCCC1)C1CCCCC1>[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17](=[O:20])[CH:18]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[CH3:19]

Participants

7

Reactant 3

HCID 121674-ChloroanisoleHCID 5793991-(2-Fluorophenyl)propan-1-oneHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 1176415651-(2'-Fluorophenyl)-2-(4'-methoxyphenyl)-1-propanonYield 52.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 71725627(2-Dicyclohexylphosphino-3-methoxy-N-methyl-N-phenylbenzenamineCatalystHCID 1140TolueneSolvent

Procedure

This reaction is carried out in the same manner as the reaction in example 3. The difference is that, the reactants are p-methoxyphenyl chloride (142.3 mg, 1.0 mmol), 1-(2-fluorophenyl)-1-propanone (304.2 mg, 2.0 mmol), palladium acetate (6.8 mg, 0.030 mmol), 2-Methoxy-6-(N-methyl-N-phenyl-amino)phenyl(dicyclohexyl)phosphine (18.4 mg, 0.045 mmol), t-BuONa (192.7 mg, 2.0 mmol) in 3 mL dry toluene at 110° C. for 41.5 h. 1-(2′-Fluorophenyl)-2-(4′-methoxyphenyl)-1-propanon (134.7 mg) was obtained with a yield of 52% as liquid. 1H NMR (300 MHz, CDCl3) δ 7.76-7.68 (m, 1H, ArH), 7.44-7.34 (m, 1H, ArH), 7.20-7.08 (m, 3H, ArH), 7.07-6.98 (m, 1H, ArH), 6.83-6.77 (m, 2H, ArH), 4.57 (q, J=6.9 Hz, 1H, CH), 3.73 (s, 3H, OCH3), 1.52 (d, J=6.9 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 199.8 (d, J=3.8 Hz), 160.7 (d, J=251.9 Hz), 158.5, 133.8 (d, J=8.8 Hz), 132.3, 130.9 (d, J=2.8 Hz), 129.1, 126.0 (d, J=12.8 Hz), 124.2 (d, J=3.9 Hz), 116.4 (d, J=23.7 Hz), 114.0, 55.0, 50.9 (d, J=5.9 Hz), 18.8; 19F NMR (282 MHz, CDCl3) 6-100.1; IR (neat) v (cm−1) 3069, 3034, 2974, 2933, 2871, 2836, 1682, 1609, 1582, 1513, 1480, 1451, 1422, 1373, 1324, 1303, 1274, 1254, 1211, 1179, 1153, 1105, 1034, 1005; MS (70 eV, EI) m/z (%): 259 (M++1, 0.99), 258 (M+, 5.49), 135 (100); HRMS calcd for C16H15O2F (M+): 258.1056. Found: 258.1057.

Workup

  1. customThis reaction is carried out in the same manner as the reaction in example 3
  2. customat 110° C.
  3. customfor 41.5 h

Sources & evidence

ORD record
ord-249382e38ec241b0997834116489f6d2
Source dataset
uspto-grants-2016_01
Patent number
US09243011B2

Reaction notes

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