Trimethylsilyl isocyanate → 1-(4-Methoxyphenyl)-4-[2-(5-aminocarbonylisochroman-1-yl)ethyl]piperazine

HRID 368854

반응식

HRID 368854 반응식
C([Li])(C)(C)C.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][CH:22]3[C:31]4[C:26](=[C:27](Br)[CH:28]=[CH:29][CH:30]=4)[CH2:25][CH2:24][O:23]3)[CH2:16][CH2:15]2)=[CH:10][CH:9]=1.C[Si]([N:37]=[C:38]=[O:39])(C)C>C1COCC1.O1CCOCC1>[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][CH:22]3[C:31]4[C:26](=[C:27]([C:38]([NH2:37])=[O:39])[CH:28]=[CH:29][CH:30]=4)[CH2:25][CH2:24][O:23]3)[CH2:16][CH2:15]2)=[CH:10][CH:9]=1

참가 물질

6

반응물 3

HCID 70696Trimethylsilyl isocyanateHCID 232887441-(4-Methoxyphenyl)-4-[2-(5-bromoisochroman-1-yl)ethyl]piperazineHCID 178418306HCID 178418306, 화합물

생성물 1

HCID 232888291-(4-Methoxyphenyl)-4-[2-(5-aminocarbonylisochroman-1-yl)ethyl]piperazine

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 312751,4-Dioxane용매

실험 절차

A mixture of t-butyl lithium (2 eqs, 1.7 M in hexane) in THF (2 ml/mmol bromide) is cooled to -78° for 10 minutes before adding the 1-(4-methoxyphenyl)-4-[2-(5-bromoisochroman-1-yl)ethyl]piperazine (LXXIV, EXAMPLE 100) in THF (4 ml/mmol) dropwise over 10 minutes. A freshly distilled solution of trimethylsilylisocyanate (1.5 eqs) is added via syringe as a solution in dioxane (4 volume equivalents) at once. After 15 minutes, the cooling bath is removed and the mixture allowed to warm to 20-25°. The reaction mixture is quenched with ammonium chloride, the organics are removed under reduced pressure, and the aqueous residue is extracted two times with methylene chloride, dried over sodium sulfate, filtered and concentrated. The crude material is purified by flash chromatography on silica gel. In this manner, 1-(4-methoxyphenyl)-4-[2-(5-bromoisochroman-1-yl)ethyl]piperazine (LXXIV, EXAMPLE 100, 345 mg) is converted to the corresponding amide, the title compound, mp 185-186°.

후처리

  1. temperatureis cooled to -78° for 10 minutes
  2. customthe cooling bath is removed
  3. temperatureto warm to 20-25°
  4. customThe reaction mixture is quenched with ammonium chloride
  5. customthe organics are removed under reduced pressure
  6. extractionthe aqueous residue is extracted two times with methylene chloride
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material is purified by flash chromatography on silica gel

출처 및 근거

ORD 기록
ord-c323b231d7ec4362b0bb1c6e435381a2
출처 데이터셋
uspto-grants-2000_10
특허 번호
US06133446

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