1-Naphthoic acid → 4-Methoxy-2-(6-methyl-pyridin-2-yloxy)-5-thiophen-2-yl-benzaldehyde

HRID 10751

반응식

HRID 10751 반응식
[OH:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)=[CH:6][C:3]=1[CH:4]=[O:5].Br[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=1.C1(C(O)=O)C2C(=CC=CC=2)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[O-]C1C=CC=CC=1>C1(C)C=CC=CC=1.[OH-].[Na+].C(OCC)(=O)C>[CH3:11][O:10][C:8]1[C:7]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)=[CH:6][C:3]([CH:4]=[O:5])=[C:2]([O:1][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=2)[CH:9]=1

참가 물질

9

반응물 5

HCID 68471-Naphthoic acidHCID 10796Cesium carbonate2회HCID 792052-Bromo-6-methylpyridineHCID 119047PhenolateHCID 118589982-Hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde

생성물 1

HCID 219810184-Methoxy-2-(6-methyl-pyridin-2-yloxy)-5-thiophen-2-yl-benzaldehyde수율 65.9%

시약·촉매·용매 3

HCID 1140Toluene용매2회HCID 8857Ethyl Acetate용매2회HCID 14798Sodium Hydroxide용매

반응 조건

온도
110 °C

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.

후처리

  1. additionwas added
  2. stirringstirred for 30 min
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (5×20 mL)
  5. washThe combined organic extracts were washed with a 50% brine solution (1×25 mL), brine (1×25 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to an dark brown semi-solid

출처 및 근거

ORD 기록
ord-bf7cac834a044372bd0d04983d7dc8e9
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07094801B2

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