Ammonium Chloride → Methyl 4-[cyclohexyl(5-cyclohexyl-2-ethylthiophen-3-yl)methoxy]benzoate

HRID 1877004Notes

Reaction equation

HRID 1877004 reaction equation
Br[C:2]1[S:6][C:5]([CH2:7][CH3:8])=[C:4]([CH:9]([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[O:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=2)[CH:3]=1.[Br-].[CH:28]1([Zn+])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.O1CCCC1.[Cl-].[NH4+]>CN1CCCC1=O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:21]1([CH:9]([C:4]2[CH:3]=[C:2]([CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[S:6][C:5]=2[CH2:7][CH3:8])[O:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=2)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 68516383Methyl 4-[(5-bromo-2-ethylthiophen-3-yl)(cyclohexyl)methoxy]benzoateHCID 178420634HCID 178420634, compound

Product 1

HCID 68515167Methyl 4-[cyclohexyl(5-cyclohexyl-2-ethylthiophen-3-yl)methoxy]benzoateYield 46%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of methyl 4-[(5-bromo-2-ethylthiophen-3-yl)(cyclohexyl)methoxy]benzoate (1.20 g) synthesized above in N-methylpyrrolidone (30 mL) were added 0.5M cyclohexylzinc bromide-tetrahydrofuran solution (8.22 mL) and bis(tri-tert-butylphosphine)palladium (70.0 mg) at 0° C., and the mixture was stirred for 1 hr under an argon atmosphere while heating to 80° C. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19, volume ratio) to give the title compound (0.56 g, 46%) as a colorless oil.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19, volume ratio)

Sources & evidence

ORD record
ord-3c146e2b34c64880b9ea229c33ceba6d
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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