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

HRID 478861Notes

Reaction equation

HRID 478861 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) 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).

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-5982c219e5fd4603a3c8ccf87773138c
Source dataset
uspto-grants-2003_11
Patent number
US06642266B2

Reaction notes

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