Potassium Sodium Tartrate → (S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxy-N-(pyridin-2-yl)propanamide

HRID 1098273노트

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HRID 1098273 반응식
C[Al](C)C.[N:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH2:11].[Si:12]([O:19][CH:20]1[CH2:23][N:22]([CH2:24][C@H:25]([OH:30])[C:26](OC)=[O:27])[CH2:21]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1.O>[Si:12]([O:19][CH:20]1[CH2:23][N:22]([CH2:24][C@H:25]([OH:30])[C:26]([NH:11][C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][N:5]=2)=[O:27])[CH2:21]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

참가 물질

7

반응물 4

HCID 9357Potassium Sodium TartrateHCID 104392-AminopyridineHCID 16682925TrimethylaluminumHCID 57504648(S)-methyl 3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxypropanoate

생성물 1

HCID 57504737(S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxy-N-(pyridin-2-yl)propanamide수율 85.7%

시약·촉매·용매 2

HCID 962Water용매HCID 1140Toluene용매2회

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온도
0 °C

실험 절차

Trimethylaluminium (2.384 mL, 4.77 mmol) was added to pyridin-2-amine (0.390 g, 4.15 mmol) in toluene (30 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. (S)-methyl 3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxypropanoate (Intermediate AD3) (1.2 g, 4.15 mmol) in toluene (10 mL) was added and the reaction was allowed to warm to room temperature and then heated at 80° C. for 4 hours. The reaction mixture was cooled, 20% Rochelle salt in water (75 mL) added and stirred for 2 hours. The mixture was extracted with ethyl acetate (2×5 mL) and the combined organic extracts washed with water (50 mL) and brine (50 mL), dried (MgSO4), filtered and evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in EtOAc to afford the product (1.25 g).

후처리

  1. temperatureto warm to room temperature
  2. temperatureheated at 80° C. for 4 hours
  3. temperatureThe reaction mixture was cooled
  4. stirringstirred for 2 hours
  5. extractionThe mixture was extracted with ethyl acetate (2×5 mL)
  6. washthe combined organic extracts washed with water (50 mL) and brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in EtOAc

출처 및 근거

ORD 기록
ord-c149492c26af4595b3a15d8509cbd22b
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08143263B2

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