Sodium Bicarbonate → 7-{2-[4-(4-Fluoro-phenyl)-3-hydroxy-butyl]-5-oxo-pyrrolidin-1-yl}heptanenitrile

HRID 478860Notes

Reaction equation

HRID 478860 reaction equation
C([Si](C)(C)[O:6][CH:7]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[CH2:8][CH2:9][CH:10]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]#[N:23])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C([O-])(O)=O.[Na+]>C1COCC1>[F:31][C:28]1[CH:29]=[CH:30][C:25]([CH2:24][CH:7]([OH:6])[CH2:8][CH2:9][CH:10]2[CH2:14][CH2:13][C:12](=[O:15])[N:11]2[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]#[N:23])=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 227187687-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-(4-fluoro-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-heptanenitrile

Product 1

HCID 227187637-{2-[4-(4-Fluoro-phenyl)-3-hydroxy-butyl]-5-oxo-pyrrolidin-1-yl}heptanenitrileYield 68.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-{2-[3-(tert-butyl-dimethyl-silanyloxy)-4-(4-fluoro-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-heptanenitrile (158 mg, 0.333 mmol) in THF (20 mL) at 0° C. was added TBAF (1M in THF, 0.50 mL, 0.50 mmol). The reaction mixture was stirred at room temperature for 3 h and saturated aqueous NaHCO3 was added. The volatiles were removed in vacuo. The remaining aqueous solution was washed with CHCl3 (4×5 mL) and the combined organic solutions were dried (MgSO4), filtered and concentrated. The residue was purified by medium pressure chromatography (1:1 hexanes:EtOAc to EtOAc) provided 7-{2-[4-(4-fluoro-phenyl)-3-hydroxy-butyl]-5-oxo-pyrrolidin-1-yl}-heptanenitrile (82 mg). 1H NMR (CDCl3) δ7.15 (m, 2H), 7.00 (m, 2H), 3.77 (m, 1H), 3.58 (m, 2H), 2.89 (m, 1H), 2.79 (m, 1H), 2.64 (m, 1H), 2.34 (m, 4H), 2.12 (m, 1H), 1.68-1.24 (m, 14H); MS 361.2 (M+1).

Workup

  1. customThe volatiles were removed in vacuo
  2. washThe remaining aqueous solution was washed with CHCl3 (4×5 mL)
  3. dry with materialthe combined organic solutions were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by medium pressure chromatography (1:1 hexanes:EtOAc to EtOAc)

Sources & evidence

ORD record
ord-ac5ee3ca529e425883d2bf9554893170
Source dataset
uspto-grants-2003_11
Patent number
US06642266B2

Reaction notes

Loading…