1,2-Dibromoethane → 7-Phenyl-1-[5-(Pyridin-2-Yl)-1,3,4-Oxadiazol-2-Yl]heptan-1-One

HRID 877399Notes

Reaction equation

HRID 877399 reaction equation
BrCCBr.Br[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C:24]1[O:28][C:27]([C:29](OC)=[O:30])=[N:26][N:25]=1>C1COCC1>[C:12]1([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][C:29]([C:27]2[O:28][C:24]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=3)=[N:25][N:26]=2)=[O:30])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 78391,2-DibromoethaneHCID 561788(6-Bromohexyl)benzeneHCID 59691753Methyl 5-(pyridin-2-yl)-1,3,4-oxadiazole-2-carboxylate

Product 1

HCID 114844537-Phenyl-1-[5-(Pyridin-2-Yl)-1,3,4-Oxadiazol-2-Yl]heptan-1-OneYield 52.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A dry vial was charged with freshly activated Mg turnings (115 mg, 5 mmol), 100 μL of anhydrous THF and a drop of 1,2-dibromoethane under Ar. This mixture was treated dropwise with a solution of 6-bromohexylbenzene (240 mg, 1 mmol) in THF (1 mL) at 23° C. The mixture was warmed and sonicated repeatedly until Grignard formation occurred. The gray solution of the Grignard reagent was added to a solution of methyl 5-(pyridin-2-yl)-1,3,4-oxadiazole-2-carboxylate (S7, 40 mg, 0.17 mmol) in THF (2 mL) at −40° C. Stirring was continued for 2 h before the reaction was quenched by the addition of MeOH at −40° C. The mixture was extracted with EtOAc and washed with water, saturated NaHCO3 and saturated aqueous NaCl followed by separation and evaporation. Flash chromatography (SiO2, 1×4 cm, 40% EtOAc-hexanes) afforded the title compound (30 mg, 51%) as a white solid: 1H NMR (CDCl3, 400 MHz) δ 8.85 (d, 1H, J=4.7 Hz), 8.30 (d, 1H, J=7.9 Hz), 7.93 (td, 1H, J=1.5, 7.8 Hz), 7.54 (ddd, 1H, J=0.9 4.7, 7.6 Hz), 7.26-7.30 (m, 2H), 7.16-7.19 (m, 3H), 3.31 (t, 2H, J=7.3 Hz), 2.62 (t, 2H, J=7.6 Hz), 1.82 (quintet, 2H, J=7.3 Hz), 1.66 (quintet, 2H, J=7.5 Hz), 1.43 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ 187.1, 165.0, 161.2, 150.8, 142.6 (2C), 137.3, 128.3, 128.2, 126.7, 125.6, 124.0, 40.0, 35.8, 31.2, 28.9, 28.8, 23.5; IR (film) νmax 2927, 2856, 1709, 1589, 1442, 1398, 1038, 986, 798, 754, 710 cm−1; HRMS-ESI-TOF m/z 336.1717 ([M+H]+, C20H21N3O2 requires 336.1706).

Workup

  1. temperatureThe mixture was warmed
  2. customsonicated repeatedly until Grignard formation
  3. customwas quenched by the addition of MeOH at −40° C
  4. extractionThe mixture was extracted with EtOAc
  5. washwashed with water, saturated NaHCO3 and saturated aqueous NaCl
  6. customfollowed by separation and evaporation

Sources & evidence

ORD record
ord-4649b130305942949343fae12cd83af9
Source dataset
uspto-grants-2015_03
Patent number
US08987312B2

Reaction notes

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