Triphenylphosphine → 4-(3-Cyclopentyloxy-4-methoxyphenyl)-4-(2-[3-(3-methyl-[1,2,4]oxadiazole-5-yl)phenyl]ethynyl)cyclohexan-1-one

HRID 343572Notes

Reaction equation

HRID 343572 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.I[C:25]1[CH:26]=[C:27]([C:31]2[O:35][N:34]=[C:33]([CH3:36])[N:32]=2)[CH:28]=[CH:29][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>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>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C:15]3([C:22]#[C:23][C:29]4[CH:30]=[CH:25][CH:26]=[C:27]([C:31]5[O:35][N:34]=[C:33]([CH3:36])[N:32]=5)[CH:28]=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

6

Reactant 3

HCID 11776TriphenylphosphineHCID 10828930HCID 10828930, compoundHCID 193499795-(3-Iodophenyl)-3-methyl-1,2,4-oxadiazole

Product 1

HCID 538356234-(3-Cyclopentyloxy-4-methoxyphenyl)-4-(2-[3-(3-methyl-[1,2,4]oxadiazole-5-yl)phenyl]ethynyl)cyclohexan-1-oneYield 78%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

A stirred mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-4-ethynylcyclohexan-1-one (0.200 g, 0.64 mmol) and 5-(3-iodophenyl)-3-methyl-[1,2,4]oxadiazole (0.201 g, 0.70 mmol) in dry triethylamine (4.6 mL) was treated under argon with a mixture of tetrakis(triphenylphosphine)palladium (0.032 g, 0.028 mmol), cuprous iodide (0.0067 g, 0.035 mmol), and triphenylphosphine (a small crystal) at 70° C. for 1 h and at 25° C. for 15 h. The reaction mixture was concentrated in vacuo and a solution of the residue was dissolved in methylene chloride, was treated with cold dilute hydrochloric acid and was dried over anhydrous sodium sulfate. The crude product was chromatographed (silica, 5 to 10% ethyl acetate in methylene chloride/hexanes 1:1) and the pure fractions were combined, concentrated in vacuo, crystallized from ethyl ether and dried at 60° C. in vacuo to afford the titled compound as an off-white powder (0.235 g, 78%), mp 88°-91° C. Anal. (C29H30N2O4) calcd: C 74.02, H 6.43, N 5.95, found: C 73.77, H 6.53, N 5.78.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutiona solution of the residue was dissolved in methylene chloride
  3. additionwas treated with cold dilute hydrochloric acid
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. customThe crude product was chromatographed (silica, 5 to 10% ethyl acetate in methylene chloride/hexanes 1:1)
  6. concentrationconcentrated in vacuo
  7. customcrystallized from ethyl ether
  8. customdried at 60° C. in vacuo

Sources & evidence

ORD record
ord-38fd0a7e9fce4c91934b860701c3df4e
Source dataset
uspto-grants-1999_01
Patent number
US05861421

Reaction notes

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