2,2'-Bipyridine → (Z)-ethyl 3-hydroxy-3-(2,4,5-trifluoro-3-methoxyphenyl)acrylate

HRID 1666967

반응식

HRID 1666967 반응식
C([Li])CCC.[C:6]([O:12][CH2:13][CH3:14])(=[O:11])[CH2:7][C:8]([OH:10])=O.N1C=CC=CC=1C1C=CC=CN=1.[F:27][C:28]1[C:36]([O:37][CH3:38])=[C:35]([F:39])[C:34]([F:40])=[CH:33][C:29]=1C(Cl)=O>O1CCCC1.C(OCC)(=O)C>[OH:10]/[C:8](/[C:29]1[CH:33]=[C:34]([F:40])[C:35]([F:39])=[C:36]([O:37][CH3:38])[C:28]=1[F:27])=[CH:7]\[C:6]([O:12][CH2:13][CH3:14])=[O:11]

참가 물질

7

반응물 4

HCID 14742,2'-BipyridineHCID 70615Monoethyl malonateHCID 27752812,4,5-Trifluoro-3-methoxybenzoyl chlorideHCID 178418339Butyllithium3회

생성물 1

HCID 86611032(Z)-ethyl 3-hydroxy-3-(2,4,5-trifluoro-3-methoxyphenyl)acrylate

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

Compound B is prepared using the general method of Wierenga and Skulnick (Wierenga, W.; Skulnick, H. I. J. Org. Chem. (1979) 44: 310-311). n-Butyllithium (1.6 M in hexanes) is added to a cooled (−78° C.) solution of tetrahydrofuran (10 mL) containing ethyl hydrogen malonate (180 μL, 1.50 mmol) and 2,2′-bipyridyl (˜1 mg as indicator). The temperature of the reaction mixture is allowed to rise to ca. −5° C. during the addition of n-butyllithium. Sufficient n-butyllithium (2.8 mL, 4.48 mmol) is added until a pink color persists at −5° C. for 5-10 min. A solution of 2,4,5-trifluoro-3-methoxybenzoyl chloride (0.75 mmol, vide supra) in tetrahydrofuran (˜3 mL) is added in one portion to the reaction mixture that had been recooled to −78° C. The resulting mixture is allowed to warm to room temperature, diluted with ethyl acetate (50 mL), and quenched with a 1 M aqueous solution of hydrochloric acid. The organic layer is washed with a 5% aqueous solution of sodium bicarbonate (2×30 mL), followed by brine (2×50 mL), dried over sodium sulfate, and evaporated under reduced pressure to give the crude product. This material is purified by flash column chromatography (eluting with 20% v/v ethyl acetate in hexanes) to give pure B as a white solid. 1H NMR (300 MHz, CDCl3): (enol, predominant tautomer, ≧90%) δ 1.32 (t, JH-H=7.0 Hz, 3H, CO2CH2CH3), 4.02 (apparent t, JH-F=1.0 Hz, 3H, OCH3), 4.25 (q, JH-H=7.0 Hz, 2H, CO2CH2CH3), 5.79 (s, 1H, CH3C(OH)═CH—CO2CH2CH3), 7.39 (ddd, JH-F=11.0 Hz, 8.5 Hz, 6.5 Hz, 1H, aromatic), 12.68 (s, 1H, OH). 19F{1H} NMR (282 MHz, CDCl3): δ−146.8 (dd, JF-F=21.5 Hz, 10.5 Hz, 1F), −140.2 (dd, JF-F=21.5 Hz, 13.5 Hz, 1F), −131.3 (dd, JF-F=13.5 Hz, 10.5 Hz, 1F).

후처리

  1. customhad been recooled to −78° C
  2. customquenched with a 1 M aqueous solution of hydrochloric acid
  3. washThe organic layer is washed with a 5% aqueous solution of sodium bicarbonate (2×30 mL)
  4. dry with materialdried over sodium sulfate
  5. customevaporated under reduced pressure

출처 및 근거

ORD 기록
ord-f483b8d130884ed19bb473282ec1e82d
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044204B2

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