Hydrochloric Acid → 5-[4-(4-Fluoro-phenyl)-3-hydroxy-butyl]-1-[6-(2H-tetrazol-5-yl)-hexyl]-pyrrolidin-2-one

HRID 478861ノート

反応式

HRID 478861 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([OH:26])[CH2:10][CH2:11][CH:12]2[CH2:16][CH2:15][C:14](=[O:17])[N:13]2[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]#[N:25])=[CH:4][CH:3]=1.[N:27]([Si](C)(C)C)=[N+:28]=[N-:29].C([Sn](=O)CCCC)CCC.Cl>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([OH:26])[CH2:10][CH2:11][CH:12]2[N:13]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]3[N:27]=[N:28][NH:29][N:25]=3)[C:14](=[O:17])[CH2:15][CH2:16]2)=[CH:4][CH:3]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 61221Dibutyltin oxide2 回HCID 78378Azidotrimethylsilane2 回HCID 227187637-{2-[4-(4-Fluoro-phenyl)-3-hydroxy-butyl]-5-oxo-pyrrolidin-1-yl}heptanenitrile

生成物 1

HCID 101267755-[4-(4-Fluoro-phenyl)-3-hydroxy-butyl]-1-[6-(2H-tetrazol-5-yl)-hexyl]-pyrrolidin-2-one収率 49.1%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

Following the procedure described for Example 3, Step D, 7-{2-[4-(4-fluoro-phenyl)-3-hydroxy-butyl]-5-oxo-pyrrolidin-1-yl}-heptanenitrile (71 mg, 0.197 mmol) was reacted with azidotrimethylsilane (45 mg, 0.394 mmol) and dibutyltin oxide (5 mg, 0.02 mmol) in toluene (10 mL) heated under reflux for 16 h. Additional azidotrimethylsilane (200 mg) and dibutyltin oxide (50 mg) were added and the reaction mixture was heated under reflux for 5 h. The reaction mixture was acidified with 1N HCl to pH=2 (5 mL) and the aqueous solution was washed with EtOAc (4×10 mL). The combined organic solutions were dried (MgSO4), filtered, and concentrated. Purification by medium pressure chromatography (EtOAc to 39:1 EtOAc:MeOH to 19:1 EtOAc:MeOH) provided the title compound of Example 5A (39 mg). 1H NMR (CDCl3) 67 7.16 (m, 2H), 7.00 (m, 2H), 3.81 (m, 1H), 3.68 (m,1H), 3.53 (m, 1H), 2.99 (m, 3H), 2.80 (m, 1H), 2.68 (m, 1H), 2.47 (m, 2H), 2.20 (m, 1H), 1.88-1.22 (m, 14H); MS 404.3 (M+1); 402.3 (M−1).

後処理

  1. temperatureheated
  2. temperatureunder reflux for 16 h
  3. temperaturethe reaction mixture was heated
  4. temperatureunder reflux for 5 h
  5. washthe aqueous solution was washed with EtOAc (4×10 mL)
  6. dry with materialThe combined organic solutions were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by medium pressure chromatography (EtOAc to 39:1 EtOAc:MeOH to 19:1 EtOAc:MeOH)

出典と根拠

ORDレコード
ord-5982c219e5fd4603a3c8ccf87773138c
出典データセット
uspto-grants-2003_11
特許番号
US06642266B2

反応ノート

読み込み中…