Sodium bis(trimethylsilyl)amide → 4-(3-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzoic acid methyl ester

HRID 458964Notes

Reaction equation

HRID 458964 reaction equation
[C:1]([Si:5]([CH3:24])([CH3:23])[O:6][CH:7]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:8][CH2:9][CH:10]1[NH:14][C:13](=[O:15])[CH2:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:35][O:36][C:37](=[O:48])[C:38]1[CH:43]=[CH:42][C:41]([CH2:44][CH2:45][CH2:46]Br)=[CH:40][CH:39]=1>CN(C=O)C>[CH3:35][O:36][C:37](=[O:48])[C:38]1[CH:43]=[CH:42][C:41]([CH2:44][CH2:45][CH2:46][N:14]2[C:13](=[O:15])[CH2:12][CH2:11][CH:10]2[CH2:9][CH2:8][CH:7]([O:6][Si:5]([C:1]([CH3:3])([CH3:2])[CH3:4])([CH3:24])[CH3:23])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:40][CH:39]=1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 10801120Methyl 4-(3-bromopropyl)benzoateHCID 129700855-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-pyrrolidin-2-one

Product 1

HCID 129700974-(3-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzoic acid methyl esterYield 70.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 5-[3-(tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-pyrrolidin-2-one (3.20 g, 9.21 mmol) in DMF (30 mL) at 0° C. was added NaHMDS (1M in THF, 11.5 mL, 11.5 mmol). After 1 h, 4-(3-bromo-propyl)-benzoic acid methyl ester (2.84 g, 11.0 mmol) was added and the reaction mixture was stirred at 70° C. for 18 h. The DMF was removed in vacuo and the residue was dissolved in EtOAc. The organic solution was washed with water, dried (MgSO4), filtered and concentrated. The residue was purified by medium pressure chromatography (30% EtOAc in hexanes) to yield 3.39 g of 4-(3-{2-[3-(tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzoic acid methyl ester. 1H NMR (CDCl3) (selected peaks) δ7.92 (m, 2H), 7.25–7.09 (m, 7H), 3.86 (s, 3H), 3.80 (m, 1H), 3.61 (m, 1H), 3.46 (m, 1H), 2.90 (m, 1H), 2.78–2.57 (m, 4H), 2.38–2.18 (m, 2H), 0.83 (s, 9H); MS 524.1 (M+1).

Workup

  1. customThe DMF was removed in vacuo
  2. dissolutionthe residue was dissolved in EtOAc
  3. washThe organic solution was washed with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by medium pressure chromatography (30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-22c8b8aa966542ec8fd99ab5b05527a4
Source dataset
uspto-grants-2007_03
Patent number
US07192979B2

Reaction notes

Loading…