반응 #10847

ord-bf7cac834a044372bd0d04983d7dc8e9

반응 방정식

[O-]c1ccccc1
phenoxide
O=C([O-])[O-].[Cs+].[Cs+]
cesium carbonate
COc1cc(O)c(C=O)cc1-c1cccs1
2-hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde
Cc1cccc(Br)n1
2-bromo-6-methylpyridine
O=C(O)c1cccc2ccccc12
1-naphthoic acid
O=C([O-])[O-].[Cs+].[Cs+]
cesium carbonate
COc1cc(Oc2cccc(C)n2)c(C=O)cc1-c1cccs1
4-methoxy-2-(6-methyl-pyridin-2-yloxy)-5-thiophen-2-yl-benzaldehyde
수율 65.9%

반응 조건

온도
110°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    workup.ADDITIONwas added
  2. 2
    workup.STIRRINGstirred for 30 min
  3. 3
    기타The layers were separated
  4. 4
    추출the aqueous layer was extracted with ethyl acetate (5×20 mL)
  5. 5
    세척The combined organic extracts were washed with a 50% brine solution (1×25 mL), brine (1×25 mL)
  6. 6
    건조dried over sodium sulfate
  7. 7
    농축concentrated to an dark brown semi-solid

실험 절차

Ex-122A: To a solution of 2-hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde (0.68 g, 2.9 mmol) and 2-bromo-6-methylpyridine (0.25 g, 1.4 mmol) in toluene (1.0 mL) was added ethyl acetate (0.0063 g, 0.072 mmol, 1-naphthoic acid (0.50 g, 2.9 mmol), 5 Å molecular sieves (0.36 g), cesium carbonate (0.94 g, 2.9 mmol), and copper(I) triflate-benzene complex (0.020 g, 0.036 mmol). The phenoxide crashed out of solution upon addition of cesium carbonate and additional toluene (1 mL) was added to facilitate stirring. The heterogeneous solution was immediately heated to 110° C. and aged for 24 h. Upon completion, as determined by HPLC, the reaction was diluted with a 5% sodium hydroxide solution (10 mL) and ethyl acetate (10 mL) and stirred for 30 min. The layers were separated and the aqueous layer was extracted with ethyl acetate (5×20 mL). The combined organic extracts were washed with a 50% brine solution (1×25 mL), brine (1×25 mL), dried over sodium sulfate and concentrated to an dark brown semi-solid. Silica gel chromatography (ethyl acetate/hexanes, 1:4) afforded 0.30 g (65%) of 4-methoxy-2-(6-methyl-pyridin-2-yloxy)-5-thiophen-2-yl-benzaldehyde as a light orange solid, mp 140–141° C. 1H-NMR (300 MHz, CDCl3) δ 10.21 (s, 1H), 8.23 (s, 1H), 7.64 (dd, 1H, J=7.8, 7.2 Hz), 7.52 (d, 1H, J=3.3 Hz), 7.35 (d, 1H, J=5.1 Hz), 7.10 (dd, 1H, J=5.1, 3.3 Hz), 6.94 (d, 1H, J=7.2 Hz), 6.78 (d, 1H, J=7.8 Hz), 6.75 (s, 1H), 3.92 (s, 3H), 2.44 (s, 3H). HRMS (EI) Calcd. for C18H15NO3S: 325.0773. Found: 325.0775. Anal. Calcd. C18H15NO3S: C, 66.44; H, 4.65; N, 4.30; S, 9.85. Found: C, 60.00; H, 4.58; N, 4.05; S, 9.84.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07094801B2uspto-grants-2006_08