Lithium diisopropylamide → (S)-5,11-Dihydro-5-(1-[4-methylphenylsulphonyl]-2-pyrrolidinylmethyl)dibenzo[b,e][1,4]thiazepine

HRID 1460489노트

반응식

HRID 1460489 반응식
C([N-]C(C)C)(C)C.[Li+].COC1C=CC(CCN2CCC[C@H]2C[N:23]2[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[CH2:27][S:26][C:25]3[CH:34]=[CH:35][CH:36]=[CH:37][C:24]2=3)=CC=1.[CH3:40][C:41]1[CH:46]=[CH:45][C:44]([S:47]([N:50]2[CH2:54][CH2:53][CH2:52][C@H:51]2[CH2:55]OS(C2C=CC(C)=CC=2)(=O)=O)(=[O:49])=[O:48])=[CH:43][CH:42]=1>CCCCCC.COCCOC>[CH3:40][C:41]1[CH:42]=[CH:43][C:44]([S:47]([N:50]2[CH2:54][CH2:53][CH2:52][C@H:51]2[CH2:55][N:23]2[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[CH2:27][S:26][C:25]3[CH:34]=[CH:35][CH:36]=[CH:37][C:24]2=3)(=[O:48])=[O:49])=[CH:45][CH:46]=1

참가 물질

6

반응물 3

HCID 2724682Lithium diisopropylamideHCID 9824029(S)-5,11-Dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]thiazepineHCID 10905672{(2S)-1-[(4-methylphenyl)sulfonyl]pyrrolidin-2-yl}methyl 4-methylbenzenesulfonate

생성물 1

HCID 22841645(S)-5,11-Dihydro-5-(1-[4-methylphenylsulphonyl]-2-pyrrolidinylmethyl)dibenzo[b,e][1,4]thiazepine수율 88.9%

시약·촉매·용매 2

HCID 8058Hexane용매HCID 80711,2-Dimethoxyethane용매

실험 절차

Lithium diisopropylamide (4.3 ml of a 1.5M solution in hexane) was added to a solution of 5,11-dihydrodibenzo[b,e][1,4]thiazepine (see Example 1 for source) (1.0 g) in DME (25 ml) and the mixture stirred at room temperature for 15 minutes, treated with (S)-1-(4-methylphenylsulphonyl)-2-(4-methylphenylsulphonyloxymethyl)pyrrolidine (3.9 g) (prepared by the method of P. Karrer and K. Ehrhardt, Helv. Chim. Acta, 34, 2202 (1951)), heated under reflux for 2.5 hours, allowed to cool to room temperature, quenched with 2M hydrochloric acid and extracted with ethyl acetate. The organic extract was washed with water, dried over sodium sulphate and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, performing a gradient elution initially using hexane as eluant and changing to hexane/ethyl acetate (90:10). Appropriate fractions were combined and evaporated under reduced pressure to give the title compound as a colourless solid, (0.93 g, 44%), m.p. 88°-90° C., [α]589 25 -115° (c=0.62 in ethanol).

후처리

  1. customprepared by the method of P
  2. temperatureActa, 34, 2202 (1951)), heated
  3. temperatureunder reflux for 2.5 hours
  4. temperatureto cool to room temperature
  5. customquenched with 2M hydrochloric acid
  6. extractionextracted with ethyl acetate
  7. extractionThe organic extract
  8. washwas washed with water
  9. dry with materialdried over sodium sulphate
  10. customevaporated under reduced pressure
  11. customThe residue was purified by chromatography on silica gel
  12. washa gradient elution initially using hexane as eluant
  13. customevaporated under reduced pressure

출처 및 근거

ORD 기록
ord-a5135c786e1445139372059a6deba598
출처 데이터셋
uspto-grants-1991_12
특허 번호
US05071844

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