Nitrogen → N-((S)-2-(1-(tert-butyldimethylsilyloxy)cyclobutyl)-1-(2,6-difluoro-5-neopentylpyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide

HRID 20033

반응식

HRID 20033 반응식
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[F:16][C:17]1[C:22]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:21][CH:20]=[C:19]([F:28])[N:18]=1.[Si:29]([O:36][C:37]1([CH2:41]/[CH:42]=[N:43]/[S@@:44]([C:46]([CH3:49])([CH3:48])[CH3:47])=[O:45])[CH2:40][CH2:39][CH2:38]1)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30].N#N>C1COCC1>[Si:29]([O:36][C:37]1([CH2:41][C@H:42]([NH:43][S:44]([C:46]([CH3:49])([CH3:48])[CH3:47])=[O:45])[C:20]2[C:19]([F:28])=[N:18][C:17]([F:16])=[C:22]([CH2:23][C:24]([CH3:25])([CH3:27])[CH3:26])[CH:21]=2)[CH2:40][CH2:39][CH2:38]1)([C:32]([CH3:34])([CH3:35])[CH3:33])([CH3:31])[CH3:30]

참가 물질

7

반응물 5

HCID 947NitrogenHCID 130352,2,6,6-TetramethylpiperidineHCID 673053062,6-Difluoro-3-neopentylpyridineHCID 87349348(NE,R)-N-[2-[1-[tert-butyl(dimethyl)silyl]oxycyclobutyl]ethylidene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

생성물 1

HCID 67305123N-((S)-2-(1-(tert-butyldimethylsilyloxy)cyclobutyl)-1-(2,6-difluoro-5-neopentylpyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide수율 13.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
-78 °C

실험 절차

To a three-necked RBF was added 2,2,6,6-tetramethylpiperidine (0.34 ml, 2 mmol), THF (10 mL), and an ethanol/N2 bath. After cooling to −78° C., butyllithium (0.70 ml, 2 mmol) was added dropwise. After stirring for several minutes, the solution was cooled to −100° C. of 2,6-difluoro-3-neopentylpyridine (0.230 g, 1 mmol) in THF (2 mL) was added dropwise. The solution was then treated with (R,E)-N-(2-(1-(tert-butyldimethylsilyloxy)cyclobutyl)ethylidene)-2-methylpropane-2-sulfinamide (0.71 g, 2 mmol) in THF (3 mL). After the addition was complete the reaction was allowed to warm to 0° C. as the liquid N2 boiled off. The reaction was then quenched with water (10 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were concentrated in vacuo and adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with 1% to 20% EtOAc in hexane, to provide N-((S)-2-(1-(tert-butyldimethylsilyloxy)cyclobutyl)-1-(2,6-difluoro-5-neopentylpyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide (0.07 g, 11% yield). This material was used without further purification in the next step. MS m/z: 517 (M+1).

후처리

  1. additionwas added dropwise
  2. additionAfter the addition
  3. customThe reaction was then quenched with water (10 mL)
  4. extractionextracted with EtOAc (3×20 mL)
  5. concentrationThe combined organic layers were concentrated in vacuo
  6. customchromatographed through a Redi-Sep® pre-packed silica gel column (12 g)
  7. washeluting with 1% to 20% EtOAc in hexane

출처 및 근거

ORD 기록
ord-340cafff58344662a2a3d3509e5ab179
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745484B2

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