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

HRID 1098273ノート

反応式

HRID 1098273 の反応式
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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 1140Toluene溶媒2 回

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c149492c26af4595b3a15d8509cbd22b
出典データセット
uspto-grants-2012_03
特許番号
US08143263B2

反応ノート

読み込み中…