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

HRID 1582661Notes

Reaction equation

HRID 1582661 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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) δ7.16 (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).

Workup

  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)

Sources & evidence

ORD record
ord-dd232c1fccbf4e4cb73c8f40d94a2c21
Source dataset
uspto-grants-2004_05
Patent number
US06737437B2

Reaction notes

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