Tetrahydrofuran → HCID 16735159, compound

HRID 386426Notes

Reaction equation

HRID 386426 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[O:11][CH:10]=[N:9][CH:8]=1.[Li][CH2:13][CH2:14][CH2:15][CH3:16].[OH:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][C:26](Cl)=[O:27])=[CH:20][CH:19]=1.[CH2:29]1[CH2:33]OC[CH2:30]1>[Cl-].[Cl-].[Zn+2].[Cu]I>[O:27]=[C:26]([C:10]1[O:11][C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[CH:8][N:9]=1)[CH2:25][CH2:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][CH2:16][C:15]2[CH:33]=[CH:29][CH:30]=[CH:13][CH:14]=2)=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 7371945-(2-Pyridyl)oxazoleHCID 86645812HCID 86645812, compoundHCID 178418339Butyllithium

Product 1

HCID 16735159HCID 16735159, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3007855ZincchlorideCatalyst

Conditions

Temperature
-78 °C

Procedure

A solution of 5-(2-pyridyl)oxazole (Saikachi, H., et al. Chem. Pharm. Bull. 1969, 27, 793-796; 116 mg, 0.794 mmol) in anhydrous THF (4 mL) at −78° C. was treated dropwise with a solution of n-BuLi in hexanes (1.6 M, 0.64 mL, 0.953 mmol) under N2 and the resulting solution was stirred at −78° C. for 35 min. A solution of ZnCl2 in THF (0.5 M, 1.9 mL, 1.56 mmol) was added and the mixture was allowed to warm to 0° C. After stirring at 0° C. for 45 min, CuI (160 mg, 0.840 mmol) was added. After the mixture was stirred at 0° C. for 15 min, a solution of 3-(4-hydroxyphenyl)propanoyl chloride (1.2 equiv; prepared from 3-(4-(benzyloxy)phenyl)propanoic acid and oxalyl chloride) in anhydrous THF (1.5 mL) was added dropwise, and the mixture was stirred for an additional 1 h. The reaction mixture was quenched with addition of saturated aqueous NaHCO3 and extracted with EtOAc. The organic layer was filtered through diatomaceous earth, dried over anhydrous Na2SO4, filtered and evaporated to yield the crude product. Column chromatography (SiO2, 2.5×5 cm, 10-30% EtOAc-hexanes gradient) followed by PTLC (SiO2, 50% EtOAc-hexanes) afforded the title compound (33%) as a white solid: mp 99-100° C. 1H NMR (CDCl3, 400 MHz) 8.67 (app d, J=4.4 Hz, 1H), 7.88 (s, 1H), 7.87-7.85 (m, 1H), 7.81 (td, 1H, J=7.8, 1.8 Hz), 7.44 (d, 2H, J=7.0 Hz), 7.39 (t, 2H, J=7.5 Hz), 7.32 (t, 2H, J=6.8 Hz), 7.19 (d, 2H, J=8.5 Hz), 6.91 (d, 2H, J=8.5 Hz), 5.04 (s, 2H), 3.44 (t, 2H, J=7.4 Hz), 3.06 (t, 2H, J=7.4 Hz); 13C NMR (CDCl3, 100 MHz) 187.4, 157.2 (2C), 153.2, 150.1, 146.2, 137.1, 137.0, 132.7, 129.4, 128.5, 127.9, 127.4, 126.9, 124.2, 120.4, 114.9, 70.0, 40.9, 28.9; IR (film) νmax 3097, 2919, 1693, 1602, 1582, 1514, 1470, 1427, 1382, 1253, 1177, 1042, 963, 938, 785, 741, 697 cm−1; ESI-TOF m/z 385.1549 (C24H20N2O3+H+ requires 385.1547).

Workup

  1. temperatureto warm to 0° C
  2. stirringAfter stirring at 0° C. for 45 min
  3. stirringAfter the mixture was stirred at 0° C. for 15 min
  4. stirringthe mixture was stirred for an additional 1 h
  5. customThe reaction mixture was quenched with addition of saturated aqueous NaHCO3
  6. extractionextracted with EtOAc
  7. filtrationThe organic layer was filtered through diatomaceous earth
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customto yield the crude product

Sources & evidence

ORD record
ord-111584b818534f139be34013495a78c0
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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