2,2,6,6-Tetramethylpiperidine → N-((S)-2-(1-(tert-Butyldimethylsilyloxy)-3-methylcyclobutyl)-1-(2-fluoro-5-neopentylpyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide

HRID 20052

반응식

HRID 20052 반응식
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:19][N:18]=1.[Si:28]([O:35][C:36]1([CH2:41]/[CH:42]=[N:43]/[S:44]([C:46]([CH3:49])([CH3:48])[CH3:47])=[O:45])[CH2:39][CH:38]([CH3:40])[CH2:37]1)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29].[NH4+].[Cl-]>C1COCC1>[Si:28]([O:35][C:36]1([CH2:41][C@H:42]([NH:43][S:44]([C:46]([CH3:47])([CH3:49])[CH3:48])=[O:45])[C:22]2[C:17]([F:16])=[N:18][CH:19]=[C:20]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:21]=2)[CH2:39][CH:38]([CH3:40])[CH2:37]1)([C:31]([CH3:34])([CH3:32])[CH3:33])([CH3:30])[CH3:29]

참가 물질

7

반응물 5

HCID 130352,2,6,6-TetramethylpiperidineHCID 25517Ammonium ChlorideHCID 575158452-Fluoro-5-neopentylpyridineHCID 87349189(NE)-N-[2-[1-[tert-butyl(dimethyl)silyl]oxy-3-methylcyclobutyl]ethylidene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

생성물 1

HCID 67304601N-((S)-2-(1-(tert-Butyldimethylsilyloxy)-3-methylcyclobutyl)-1-(2-fluoro-5-neopentylpyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide수율 61.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

2,2,6,6-Tetramethylpiperidine (2.47 ml, 14.7 mmol) was dissolved in 100 ml THF and cooled to −78° C. 1-Butyllithium (5.23 ml, 13.1 mmol, 2.5M) was added and the reaction was allowed to warm up to 0° C. for 5 min before it was cooled back to −78° C. again. At this point, a solution of 2-fluoro-5-neopentylpyridine (1.75000 g, 10.5 mmol) was added dropwise and the reaction was stirred for 1 h. Next, a solution of (E)-N-(2-(1-(tert-butyldimethylsilyloxy)-3-methylcyclobutyl)ethylidene)-2-methylpropane-2-sulfinamide (3.98 g, 11.5 mmol) in THF was added dropwise and stirring was continued for 1 h. The mixture was hydrolyzed with NH4Cl in the cold, warmed up to RT extracted with EtOAc (3×150 ml), dried over MgSO4 and evaporated. N-((S)-2-(1-(tert-Butyldimethylsilyloxy)-3-methylcyclobutyl)-1-(2-fluoro-5-neopentylpyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide (3.30 g, 61.5% yield) was obtained after glass col. Chrom. (20-70% EtOAc in Hex.). Low yield due to the formation of a minor diastereomer at the NH center (approx 30%). Mixture of cis/trans at the cyclobutylring (4:1).

후처리

  1. temperatureto warm up to 0° C. for 5 min before it
  2. temperaturewas cooled back to −78° C. again
  3. stirringstirring
  4. waitwas continued for 1 h
  5. temperaturewarmed up to RT
  6. extractionextracted with EtOAc (3×150 ml)
  7. dry with materialdried over MgSO4
  8. customevaporated

출처 및 근거

ORD 기록
ord-e6a37d8afd364451a9896e9ae3853672
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745484B2

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