Dicyclohexylcarbodiimide → 4-[5-(2-Cyclopentyl-6-methoxy-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenol

HRID 245102Notes

Reaction equation

HRID 245102 reaction equation
[CH:1]1([C:6]2[CH:7]=[C:8]([CH:12]=[C:13]([O:15][CH3:16])[N:14]=2)[C:9]([OH:11])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:17]([C:19]1[CH:20]=[C:21]([CH:26]=[C:27]([CH3:30])[C:28]=1[OH:29])[C:22]([NH:24]O)=[NH:23])[CH3:18].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[CH:1]1([C:6]2[CH:7]=[C:8]([C:9]3[O:11][N:24]=[C:22]([C:21]4[CH:26]=[C:27]([CH3:30])[C:28]([OH:29])=[C:19]([CH2:17][CH3:18])[CH:20]=4)[N:23]=3)[CH:12]=[C:13]([O:15][CH3:16])[N:14]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 58418037HCID 58418037, compoundHCID 178436626HCID 178436626, compound

Product 1

HCID 1363910154-[5-(2-Cyclopentyl-6-methoxy-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenolYield 73.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-cyclopentyl-6-methoxy-isonicotinic acid (21.0 g, 102 mmol), 3-ethyl-4,N-dihydroxy-5-methyl-benzamidine (20.0 g, 103 mmol) and HOBt (1.24 g, 9 mmol) in THF (200 mL) is cooled to 5° C. before a solution of DCC (20.0 g, 97 mmol) in THF (100 mL) is added dropwise. Upon complete addition, the mixture is stirred at rt for 18 h then at 75° C. for 48 h. The solvent is evaporated and the remaining residue is dissolved in TBME (200 mL). The precipitate that forms is removed, filtered off and washed with additional TBME (200 mL). The filtrate is washed with approximately 4% aq. NaHCO3 solution (100 mL) and water (100 mL) and concentrated. The crude product is recrystallised from hot acetonitrile (200 mL) to give 4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (28.6 g) as a white solid; 1H NMR (CDCl3): δ1.33 (t, J=7.5 Hz, 3H), 1.70-1.80 (m, 2H), 1.84-1.96 (m, 4H), 2.05-2.16 (m, 2H), 2.36 (s, 3H), 2.74 (q, J=7.3 Hz, 2H), 3.25 (quint, J=7.5 Hz, 1H), 4.02 (s, 3H), 5.01 (s), 7.31 (s, 1H), 7.51 (s, 1H), 7.85 (s, 2H).

Workup

  1. additionis added dropwise
  2. additionUpon complete addition
  3. waitat 75° C. for 48 h
  4. customThe solvent is evaporated
  5. dissolutionthe remaining residue is dissolved in TBME (200 mL)
  6. customThe precipitate that forms is removed
  7. filtrationfiltered off
  8. washwashed with additional TBME (200 mL)
  9. washThe filtrate is washed with approximately 4% aq. NaHCO3 solution (100 mL) and water (100 mL)
  10. concentrationconcentrated
  11. customThe crude product is recrystallised from hot acetonitrile (200 mL)

Sources & evidence

ORD record
ord-a34bc17476384ee59354b67b2d6b7d5d
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

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