Ethanethiol → [2-(3-Fluoro-4-hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone

HRID 609808Notes

Reaction equation

HRID 609808 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[S:14][C:13]3[CH:15]=[C:16]([O:19]C)[CH:17]=[CH:18][C:12]=3[C:11]=2[C:21]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)=[CH:25][CH:24]=2)=[O:22])[CH:5]=[CH:6][C:7]=1[O:8]C.C(S)C.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[S:14][C:13]3[CH:15]=[C:16]([OH:19])[CH:17]=[CH:18][C:12]=3[C:11]=2[C:21]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)=[CH:25][CH:24]=2)=[O:22])[CH:5]=[CH:6][C:7]=1[OH:8]

Participants

5

Reactant 3

HCID 6343EthanethiolHCID 6451240Aluminum(III) ChlorideHCID 11752718[2-(3-Fluoro-4-methoxyphenyl)-6-methoxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone

Product 1

HCID 9935356[2-(3-Fluoro-4-hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanoneYield 39.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of the product of Example 1 (0.65 g, 1.25 mmol), ethanethiol (0.46 mL, 6.32 mmol), and aluminum chloride (1.17 g, 8.78 mmol) in anhydrous CH2Cl2 (20 mL) was stirred for 3.5 h. The mixture was quenched with saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicaronate and brine, dried (sodium sulfate), and concentrated. The residue was purified by chromatography (silica gel, 5-10% MeOH in CH2Cl2) and crystallized from MeOH/CH2Cl2 to give 240 mg (39%) of the title product as a yellow solid: 1H NMR (MeOD-d4) d 1.62 (m, 2H), 1.80 (m, 4H), 3.11 (m, 4H), 3.34 (t, J=6.0 Hz, 2H), 4.32 (t, J=6.0 Hz, 2H), 4.86 (br s, 2H), 6.75 t, J=8.6 Hz, 1H), 6.88 (dd, J=2.2 Hz, 8.8 Hz, 1H), 6.92 (d, J=8.8 Hz, 2H), 6.97-7.06 (m, 3H), 7.27 (d, J=2.2 Hz, 1H), 7.43 (d, J=8.8 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H); 13C NMR (DMSO-d6) d 21.8, 23.1, 53.0, 63.4, 107.1, 114.6, 115.4, 115.7, 116.0, 118.1, 123.4, 124.2, 125.0, 130.0, 130.4, 131.8, 131.9, 138.9, 139.3, 145.3, 145.5, 148.9, 152.1, 155.7, 162.0, 192.3; MS (FD) m/e 492 (MH+); Anal. calc'd. for C28H26FNO4S.0.75 H2O: C, 66.57; H, 5.65; N, 2.77. Found: C, 66.68; H, 5.78; N, 2.74.

Workup

  1. customThe mixture was quenched with saturated sodium bicarbonate
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated sodium bicaronate and brine
  4. dry with materialdried (sodium sulfate)
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (silica gel, 5-10% MeOH in CH2Cl2)
  7. customcrystallized from MeOH/CH2Cl2

Sources & evidence

ORD record
ord-83f9fe1a248c41c3aed40ceb6b797187
Source dataset
uspto-grants-1999_12
Patent number
US05998442

Reaction notes

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