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

HRID 1098281ノート

反応式

HRID 1098281 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 72.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 1140Toluene溶媒2 回

反応条件

温度
0 °C

実験手順

Trimethylaluminium (7.60 mL, 15.20 mmol) was added to pyridin-2-amine (1.431 g, 15.20 mmol) in anhydrous 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) (2.2 g, 7.60 mmol) in anhydrous toluene (10 mL) was added and the resulting solution was allowed to warm to room temperature and then heated at 80° C. for 4 hours. The mixture was cooled to room temperature, neutralised with Rochelle salt in water (20%, 75 mL), diluted with water (50 mL) and extracted with EtOAc (2×50 mL). The organic phase was separated, washed with brine, dried over MgSO4, filtered and evaporated. The crude product was purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane to give impure product. This was shown to contain the starting amine so was re-purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM to afford the product (1.928 g, 72.2%).

後処理

  1. temperatureto warm to room temperature
  2. temperatureheated at 80° C. for 4 hours
  3. temperatureThe mixture was cooled to room temperature
  4. extractionextracted with EtOAc (2×50 mL)
  5. customThe organic phase was separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane
  11. customto give impure product
  12. customso was re-purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM

出典と根拠

ORDレコード
ord-174eeb59356a4bbaa9d2e0a02dfa2d9b
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…