Tetrahydrofuran → [2-(3-Fluoro-4-methoxyphenyl)-6-methoxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone

HRID 609807

Reaction equation

HRID 609807 reaction equation
CN(C)[C:3]1[S:4][C:5]2[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:6]=2[C:7]=1[C:8]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[CH:12][CH:11]=1)=[O:9].C1COCC1.[F:37][C:38]1[CH:39]=[C:40]([Mg]Br)[CH:41]=[CH:42][C:43]=1[O:44][CH3:45]>ClC1C=CC=CC=1>[F:37][C:38]1[CH:39]=[C:40]([C:3]2[S:4][C:5]3[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:6]=3[C:7]=2[C:8]([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[CH:14][CH:15]=2)=[O:9])[CH:41]=[CH:42][C:43]=1[O:44][CH3:45]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 9954835[2-Dimethylamino-6-methoxybenzothien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanoneHCID 178491915HCID 178491915, compound

Product 1

HCID 11752718[2-(3-Fluoro-4-methoxyphenyl)-6-methoxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanoneYield 44%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Procedure

A solution of [2-dimethylamino-6-methoxybenzothien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone (1.5 g, 3.6 mmol)(see U.S. Pat. No. 5,420,349) in chlorobenzene (15 mL) was cooled to 0° and treated with a 0.73 M THF solution of 3-fluoro-4-methoxyphenylmagnesium bromide (16.0 mL, 11.7 mmol)(prepared from 4-bromo-2-fluoroanisole, catalytic iodine, and magnesium turnings in THF). The mixture was allowed to warm to ambient temperature and when the starting material was consumed, the reaction was quenched with water and extracted with ethyl acetate. The organic layer was washed with water (2x), and brine (2x), dried (sodium sulfate), and concentrated. The residue was purified via chromatography (silica gel, 5-10% MeOH in CH2Cl2) to provide 0.79 g (44%) of the title compound as a brown oil: 1H NMR d 1.44 (m, 2H), 1.59 (m, 4H), 2.48 (m, 4H), 2.74 (t, J=6.0 Hz, 2H), 3.83 (s, 3H), 3.88 (s, 3H), 4.09 (t, J=6.0 Hz, 2H), 6.77-6.83 (m, 3H), 6.96 (dd, J=2.3 Hz, 8.9 Hz, 1H), 7.11-7.19 (m, 2H), 7.31 (d, J=2.3 Hz, 1H), 7.50 (d, J=8.8 Hz, 1H), 7.75 (d, J=8.8 Hz, 2H); 13C NMR d 24.4, 26.1, 55.3, 55.9, 56.4, 57.9, 66.5, 104.7, 113.5, 114.6, 115.3, 116.7, 117.0, 124.4, 125.5, 126.7, 126.8, 130.5, 131.6, 132.6, 134.1, 140.4, 140.9, 148.0, 148.1, 153.8, 158.1, 163.5, 193.2; MS (FD) m/e 519 (M+); Anal. calc'd. for C30H30FNO4S: C, 69.34; H, 5.82; N, 2.69. Found: C, 69.63; H, 5.89; N, 2.64.

Workup

  1. customwhen the starting material was consumed
  2. customthe reaction was quenched with water
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water (2x), and brine (2x)
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated
  7. customThe residue was purified via chromatography (silica gel, 5-10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-24167da908f64ae9a07dd9740901e869
Source dataset
uspto-grants-1999_12
Patent number
US05998442

Linked notes

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