Ammonium Chloride → 4-(3-Cyclopentyloxy-4-methoxyphenyl)-4-[5-(5-methyl-[1,2,4]oxadiazol-2-yl)thien-2-ylethynyl]cyclohexan-1-one

HRID 343559Notes

Reaction equation

HRID 343559 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C:15]3([C:22]#[CH:23])[CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:25]1[S:26][C:27]([N:30]2[CH2:34][N:33]=[C:32]([CH3:35])[O:31]2)=[CH:28][CH:29]=1.[Cl-].[NH4+]>C(N(CC)CC)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C:15]3([C:22]#[C:23][C:25]4[S:26][C:27]([N:30]5[CH2:34][N:33]=[C:32]([CH3:35])[O:31]5)=[CH:28][CH:29]=4)[CH2:16][CH2:17][C:18](=[O:21])[CH2:19][CH2:20]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 3

HCID 25517Ammonium ChlorideHCID 108289304-(3-Cyclopentyloxy-4-methoxyphenyl)-4-ethynylcyclohexan-1-oneHCID 696901172-Bromo-5-(5-methyl-[1,2,4]oxadiazol-2-yl)thiophene

Product 1

HCID 867536214-(3-Cyclopentyloxy-4-methoxyphenyl)-4-[5-(5-methyl-[1,2,4]oxadiazol-2-yl)thien-2-ylethynyl]cyclohexan-1-one

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

To a solution of 4-(3-cyclopentyloxy-4-methoxyphenyl)-4-ethynyl-cyclohexan-1-one (0.17 g, 0.88 mmol) and 2-bromo-5-(5-methyl-[1,2,4]oxadiazol-2-yl)thiophene (0.18 g, 1.2 mmol) in triethylamine (5 mL) under an argon atmosphere were added tetrakis(triphenylphosphine)palladium(0) (0.037 g, 4%) and copper(I) iodide (0.010 g, 6%), and the mixture was heated at 85°-90° C. for 2 h. Ammonium chloride was added and the mixture was extracted three times with dichloromethane, was dried (magnesium sulfate) and was evaporated. Purification by flash chromatography, eluting with 25:75 ethyl acetate:hexanes, provided 4-(3-cyclopentyloxy-4-methoxyphenyl)-4-[5-(5-methyl-[1,2,4]oxadiazol-2-yl)thien-2-ylethynyl]cyclohexan-1-one as a white wax (0.17 g, 45%), mp 94°-95° C. Anal. (C27H28N2O4S) calcd: C, 68.04; H, 5.92; N, 5.88; found: C, 67.83; H, 5.89; N, 5.92.

Workup

  1. temperaturethe mixture was heated at 85°-90° C. for 2 h
  2. extractionthe mixture was extracted three times with dichloromethane
  3. dry with materialwas dried (magnesium sulfate)
  4. customwas evaporated
  5. customPurification by flash chromatography
  6. washeluting with 25:75 ethyl acetate

Sources & evidence

ORD record
ord-48f9e8820ff7430894cb56e29f04a335
Source dataset
uspto-grants-1999_01
Patent number
US05861421

Reaction notes

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