Diethyl Ether → 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-4-ol

HRID 1615517Notes

Reaction equation

HRID 1615517 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[S:11][C:10]3[CH2:12][CH2:13][CH2:14][CH2:15][C:16](=[O:17])[C:9]=3[CH:8]=2)=[CH:3][CH:2]=1.O1[CH2:22][CH2:21][CH2:20][CH2:19]1.CCO[CH2:26][CH3:27].[NH4+].[Cl-:29]>ClC1C=CC([Mg]Br)=CC=1.C(OCC)(=O)C>[Cl:29][C:19]1[CH:27]=[CH:26][C:22]([C:16]2([OH:17])[C:9]3[CH:8]=[C:7]([C:4]4[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=4)[S:11][C:10]=3[CH2:12][CH2:13][CH2:14][CH2:15]2)=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 68183156HCID 68183156, compound

Product 1

HCID 681831404-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-4-olYield 83.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 178478191HCID 178478191, compoundSolvent

Procedure

To a solution of [2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-4-one (1.44 g, 5.92 mmol) in tetrahydrofuran (30.0 mL, 400 mmol), 4-chlorophenyl magnesium bromide in ether (1M, 8.00 mL, 8.00 mmol) was added and the mixture was stirred for 40 min at rt. To the mixture were added a saturated aqueous solution of NH4Cl (10 mL) and ethyl acetate (10 mL). The resulting biphasic mixture was vigorously stirred for 15 min then the organic layer was separated. The organic phase was washed with brine (10 mL) then dried over anhydrous MgSO4. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography (SiO2, elution with 0-100% ethyl acetate/dichloromethane) to give the title compound as a yellow foam (1.76 g, 83.6% yield). LCMS: (FA) ES+ , 356. 1H NMR (400 MHz, DMSO-d6) δ: 8.47-8.57 (dd, J=1.7 Hz, J=4.5 Hz, 2H), 7.43-7.46 (m, 3H), 7.34-7.40 (m, 2H), 7.21-7.28 (m, 2H), 5.88-5.90 (br s, 1H), 2.86-3.0 (m, 1H), 2.65-2.80 (m, 1H), 2.20-2.35 (m, 1H), 1.95-2.10 (m, 1H), 1.55-1.80 (m, 3H), 1.20-1.40 (m, 1H).

Workup

  1. stirringThe resulting biphasic mixture was vigorously stirred for 15 min
  2. customthe organic layer was separated
  3. washThe organic phase was washed with brine (10 mL)
  4. dry with materialthen dried over anhydrous MgSO4
  5. customInsoluble materials were removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe obtained residue was purified by column chromatography (SiO2, elution with 0-100% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-dd3c29a3d5344775a08b22c97a278188
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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