3-Azabicyclo[3.2.2]nonane → HCID 66630350、化合物

HRID 555388ノート

反応式

HRID 555388 の反応式
C(OC([N:8]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:22])=O)=[CH:16][CH:15]=2)[CH2:9]1)=O)(C)(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH:44]12[CH2:52][CH2:51][CH:48]([CH2:49][CH2:50]1)[CH2:47][NH:46][CH2:45]2.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:44]12[CH2:52][CH2:51][CH:48]([CH2:49][CH2:50]1)[CH2:47][N:46]([C:20]([C:17]1[CH:16]=[CH:15][C:14]([O:13][CH:10]3[CH2:11][CH2:12][NH:8][CH2:9]3)=[CH:19][CH:18]=1)=[O:22])[CH2:45]2

参加物

7

反応物 5

HCID 92403-Azabicyclo[3.2.2]nonaneHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 227098074-({1-[(Tert-butoxy)carbonyl]pyrrolidin-3-yl}oxy)benzoic acid

生成物 1

HCID 66630350HCID 66630350、化合物収率 55%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 3-(4-carboxy-phenoxy)-pyrrolidine-1-carboxylic acid t-butyl ester (2.0 g, 6.53 mmol) in DMF (75 mL) was added HOBt (1.1 g, 7.83 mmol) and EDAC (1.5 g, 7.83 mmol) and the resulting mixture was stirred for 10 min. 3-Aza-bicyclo-[3.2.2]nonane (1 g, 7.83 mmol) and DIPEA (1.4 mL) were added and stirring was continued for 16 hrs at ambient temperature. The volatiles were evaporated in vacuo and to the residue was added water (50 mL) and diethyl ether (25 mL). A precipitate was forme, filtered off and redissolved in DCM (25 mL) followed by addition of TFA (10 mL). The mixture was stirred at room temperature for 16 hrs and the volatiles evaporated in vacuo. The residue was dissolved in water (50 mL) and washed with diethyl ether (2×10 mL). The pH of the aqueous phase was adjusted to ˜11 by addition of 32% NaOH followed by extraction with diethyl ether (2×50 mL). The combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo. The crude residue was stirred with EtOAc (20 mL) and the precipitate formed was filtered off. The filtrate was evaporated to dryness affording crude 1.1 g (55%) of (3-aza-bicyclo[3.2.2]non-3-yl)-[4-(pyrrolidin-3-yloxy)-phenyl]-methanone which was used without further purification.

後処理

  1. stirringstirring
  2. waitwas continued for 16 hrs at ambient temperature
  3. customThe volatiles were evaporated in vacuo and to the residue
  4. additionwas added water (50 mL) and diethyl ether (25 mL)
  5. filtrationfiltered off
  6. dissolutionredissolved in DCM (25 mL)
  7. additionfollowed by addition of TFA (10 mL)
  8. stirringThe mixture was stirred at room temperature for 16 hrs
  9. customthe volatiles evaporated in vacuo
  10. dissolutionThe residue was dissolved in water (50 mL)
  11. washwashed with diethyl ether (2×10 mL)
  12. additionThe pH of the aqueous phase was adjusted to ˜11 by addition of 32% NaOH
  13. extractionfollowed by extraction with diethyl ether (2×50 mL)
  14. dry with materialThe combined organic phases were dried (Na2SO4)
  15. filtrationfiltered
  16. customevaporated in vacuo
  17. stirringThe crude residue was stirred with EtOAc (20 mL)
  18. customthe precipitate formed
  19. filtrationwas filtered off
  20. customThe filtrate was evaporated to dryness

出典と根拠

ORDレコード
ord-1163f86b02fb4bd6b78a894047ce7989
出典データセット
uspto-grants-2011_11
特許番号
US08053447B2

反応ノート

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