Acetonitrile → 3-[3-(6-Methyl-pyridazin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

HRID 498234노트

반응식

HRID 498234 반응식
CO[C:3](=[O:17])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[N:11]=[N:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[CH:5]=1.[C:18]([C:21]1C=C(B(O)O)C=CC=1)([OH:20])=[O:19].ClC1N=N[C:34]([CH3:37])=[CH:35]C=1.O=S(Cl)Cl.[C:42](#N)C>C([O-])([O-])=O.[Na+].[Na+]>[C:34]([O:20][C:18](=[O:19])[CH2:21][C:3]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[N:11]=[N:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[CH:5]=1)=[O:17])([CH3:35])([CH3:37])[CH3:42]

참가 물질

7

반응물 5

HCID 6342AcetonitrileHCID 24386Thionyl ChlorideHCID 2272543-Chloro-6-methylpyridazineHCID 27339573-Carboxyphenylboronic acidHCID 69489500Methyl 3-(6-methylpyridazin-3-yl)benzoate

생성물 1

HCID 694864463-[3-(6-Methyl-pyridazin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

시약·촉매·용매 1

HCID 10340Sodium Carbonate용매

실험 절차

The title compound was prepared from 3-(6-methyl-pyridazin-3-yl)-benzoic acid methyl ester [prepared by the following procedure: A mixture of 3-carboxyphenylboronic acid (2.24 g, 13.5 mmol) and 3-chloro-6-methylpyridazine (1.79 g, 13.5 mmol) in acetonitrile (67 mL) and 0.4M Na2CO3-solution (67 mL) was degassed and Pd(Ph3P)4 (0.78 g, 5 mol %) was added. The reaction mixture was refluxed for 16 h, evaporated to dryness (cf. Synlett 2000, 829). The residue was suspended in MeOH (200 mL) and SOCl2 (4.9 mL, 67.5 mmol) was added dropwise at 23° C. and the reaction mixture was refluxed for 16 h. Evaporated to dryness, taken up in EtOAc, washed with sat. NaHCO3-solution and brine, dried over Na2SO4. Removal of the solvent in vacuum left a brown oil, which was purified by silica gel column chromatography with cyclohexane/EtOAc.] (2.57 g, 11.26 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a light yellow solid (2.68 g).

후처리

  1. customprepared by the following procedure
  2. customwas degassed
  3. additionPd(Ph3P)4 (0.78 g, 5 mol %) was added
  4. temperatureThe reaction mixture was refluxed for 16 h
  5. customevaporated to dryness (cf. Synlett 2000, 829)
  6. temperaturethe reaction mixture was refluxed for 16 h
  7. customEvaporated to dryness
  8. washwashed with sat. NaHCO3-solution and brine
  9. dry with materialdried over Na2SO4
  10. customRemoval of the solvent in vacuum
  11. waitleft a brown oil, which
  12. customwas purified by silica gel column chromatography with cyclohexane/EtOAc

출처 및 근거

ORD 기록
ord-20a8303ad28b4b439f681ef4e684d1c6
출처 데이터셋
uspto-grants-2005_09
특허 번호
US06949542B2

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