2-(Pyridin-2-yl)oxazole → 7-Phenyl-1-(2-(pyridin-2-yl)oxazol-5-yl)-heptan-1-ol

HRID 877396Notes

Reaction equation

HRID 877396 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[O:8][CH:9]=[CH:10][N:11]=1.[Li]CCCC.[C:17]1([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[O:30])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1>[C:17]1([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH:29]([C:9]2[O:8][C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[N:11][CH:10]=2)[OH:30])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 114577582-(Pyridin-2-yl)oxazoleHCID 148400647-PhenylheptanalHCID 178418339Butyllithium

Product 1

HCID 583662647-Phenyl-1-(2-(pyridin-2-yl)oxazol-5-yl)-heptan-1-olYield 28.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 2-(pyridin-2-yl)-oxazole (S1, 54 mg, 0.369 mmol) in THF (2 mL) was cooled to −78° C. before it was treated dropwise with 2.5 M n-BuLi (0.177 mL, 0.443 mmol). The reaction mixture was stirred at −78° C. for 20 min before 7-phenylheptanal (77 mg, 0.405 mmol) in THF (1 mL) was added dropwise. The solution was stirred for an additional 10 min at −78° C. before being warmed to room temperature. The reaction mixture was quenched with the addition of saturated aqueous NaHCO3, diluted with EtOAc and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4 and the solvent was removed under reduced pressure. Flash chromatography (SiO2, 20-70% EtOAc-hexanes) yielded the title compound (35 mg, 28%) as a colorless oil: 1H NMR (CDCl3, 500 MHz) δ 8.77 (s, 1H), 8.17 (d, 1H, J=8.0 Hz), 7.86 (t, 1H, J=8.0 Hz), 7.41 (m, 1H), 7.35-7.32 (m, 2H), 7.23 (m, 3H), 7.18 (s, 1H), 4.93 (t, 1H, J=6.5 Hz), 3.22 (br s, 1H), 2.65 (t, 2H, J=6.5 Hz), 2.01-1.98 (m, 2H), 1.68-1.66 (m, 2H), 1.44-1.42 (m, 5H); 13C NMR (CDCl3, 125 MHz) δ 160.3, 156.1, 150.2, 146.4, 143.1, 137.5, 128.8, 128.6, 126.0, 125.1, 124.9, 122.5, 66.5, 36.3, 35.8, 31.8, 29.6 (2C), 25.8.

Workup

  1. additionwas added dropwise
  2. temperaturebefore being warmed to room temperature
  3. customThe reaction mixture was quenched with the addition of saturated aqueous NaHCO3
  4. additiondiluted with EtOAc
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washThe combined organic extracts were washed with saturated aqueous NaCl
  7. dry with materialdried over Na2SO4
  8. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-961971fcece84931960187e1d6a92340
Source dataset
uspto-grants-2015_03
Patent number
US08987312B2

Reaction notes

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