Ammonium Chloride → 3-Cyclopentyloxy-4-methoxyphenylcyclohexan-1-one

HRID 343560Notes

Reaction equation

HRID 343560 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C:15]3(C#C)[CH2:20][CH2:19][C:18](=O)[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.BrC1C=C(CC(O)=[O:32])SC=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]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][C:16]3=[O:32])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 25517Ammonium ChlorideHCID 108289304-(3-Cyclopentyloxy-4-methoxyphenyl)-4-ethynylcyclohexan-1-oneHCID 212607302-(4-Bromothiophen-2-yl)acetic acid

Product 1

HCID 541944193-Cyclopentyloxy-4-methoxyphenylcyclohexan-1-oneYield 65%

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-ethynylcyclohexan-1-one (0.25 g, 0.8 mmol) and 4-bromo-2-carboxymethylthiophene (0.27 g, 1.2 mmol) in triethylamine (3.5 mL) under an argon atmosphere were added tetrakis(triphenylphosphine)palladium(0) (0.038 g, 4%) and copper(I) iodide (0.010 g, 6%), and the mixture was heated at 80°-85° C. for 0.5 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 2:8 ethyl acetate:hexanes, provided 4-(2-carbomethoxythien-4-ylethynyl)-4-(3-cyclopentyloxy-4-methoxyphenylcyclohexan-1-one as a yellow glass (0.15 g, 42%). 1H-NMR (400 MHz, CDCl3) δ 7.81 (d, J=1.3 Hz, 1H), 7.60 (d, J=1.3 Hz, 1H), 7.16 (d, J=2.2 Hz, 1H), 7.10 (dd, J=8.5, 2.2 Hz, 1H), 6.86 (d, J=8.5 Hz, 1H), 4.80 (m, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 2.98 (dt, J=14.8, 5.7 Hz, 2H), 2.48 (br d, J=14.8 Hz, 2H), 3.33 (m, 2H), 2.26 (dt, J=13.6, 4 Hz, 2H), 1.9-2.0 (m, 6H), 1.6 (m, 2H) ppm. Anal. (C26H28O5S) calcd: C, 69.00; H, 6.24; found: C, 68.82; H, 6.04.

Workup

  1. temperaturethe mixture was heated at 80°-85° C. for 0.5 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 2:8 ethyl acetate

Sources & evidence

ORD record
ord-04103caa8dbd439285c060e4ca73d9c1
Source dataset
uspto-grants-1999_01
Patent number
US05861421

Reaction notes

Loading…