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

HRID 343573Notes

Reaction equation

HRID 343573 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[S:32][C:33]([CH3:36])=[N:34][N:35]=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[S:32][C:33]([CH3:36])=[N:34][N:35]=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 108289304-(3-Cyclopentyloxy-4-methoxyphenyl)-4-ethynylcyclohexan-1-oneHCID 193499822-(3-Iodophenyl)-5-methyl-1,3,4-thiadiazole

Product 1

HCID 542762454-(3-Cyclopentyloxy-4-methoxyphenyl)-4-(2-[3-(5-methyl-[1,3,4]thiadiazol-2-yl)phenyl]ethynyl)cyclohexan-1-oneYield 82.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

A stirred mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-4-ethynylcyclohexan-1-one (0.100 g, 0.32 mmol) and 2-(3-iodophenyl)-5-methyl-[1,3,4]thiadiazole (0.097 g, 0.32 mmol) in dry triethylamine (2.5 mL) was treated under argon with a mixture of tetrakis(triphenylphosphine)palladium (0.016 g, 0.013 mmol), cuprous iodide (0.0033 g, 0.017 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 the residue was partitioned between methylene chloride and cold dilute hydrochloric acid. The organic phase was chromatographed (silica, 10 to 20% ethyl acetate in methylene chloride) and the pure fractions were combined, concentrated in vacuo and dried at 50° C. in vacuo and the brittle resin ground to afford the titled compound as a yellow powder (0.128 g, 79%). Anal. (C29H3ON2)3S.H2O) calcd: C 69.02, H 6.39, N 5.55, found: C 68.91, H 6.21, N 5.35. 1H-NMR (400 MHz, CDCl3) δ 8.06 (t, J=1.6 Hz, 1H), 7.88 (d-t, J=1.4 Hz, J=8.1 Hz, 1H), 7.58 (d-d, J=1.2 Hz, J=9.0 Hz, 1H), 7.45 (t, J=7.8 Hz), 7.21 (d, J=2.2, 1H), 7.14 (dd, J=8.4 Hz, J=2.1 Hz, 1H), 6.88 (d, J=8.5, 1H), 4.82 (p, J=4.1 Hz, 1H), 3.86 (s, 3H), 3.04 (d-t, J=6.1 Hz, J=14.2, 2H), 2.84 (s, 3H), 2.50 (d,br, J=14.9, 2H), 2.42-2.32 (m, 2H), 2.27 (d-t, J=2.8 Hz, J=14.2 Hz, 2H), 2.00-1.5 (m, 12H with H2O).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was partitioned between methylene chloride and cold dilute hydrochloric acid
  3. customThe organic phase was chromatographed (silica, 10 to 20% ethyl acetate in methylene chloride)
  4. concentrationconcentrated in vacuo
  5. customdried at 50° C. in vacuo

Sources & evidence

ORD record
ord-638ff152fe7749f4b3239135f8094fd7
Source dataset
uspto-grants-1999_01
Patent number
US05861421

Reaction notes

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