Sodium bis(trimethylsilyl)amide → N-tert-Butyl-2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-phenyl-acetamide

HRID 343149Notes

Reaction equation

HRID 343149 reaction equation
[C:1]1([N:7]2[C:13](=[O:14])[CH2:12][C:11](=[O:15])[NH:10][C:9]3[CH:16]=[CH:17][CH:18]=[CH:19][C:8]2=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:31][C:32]([N:34]([C:41]([CH3:44])([CH3:43])[CH3:42])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:33]>CN(C=O)C.C1COCC1>[C:41]([N:34]([C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C:32](=[O:33])[CH2:31][N:10]1[C:11](=[O:15])[CH2:12][C:13](=[O:14])[N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]2[CH:19]=[CH:18][CH:17]=[CH:16][C:9]1=2)([CH3:42])([CH3:43])[CH3:44]

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 10824683N-Desmethyl Dechloro ClobazamHCID 108258822-Bromo-N-tert-butyl-N-phenyl-acetamide

Product 1

HCID 10789281N-tert-Butyl-2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-phenyl-acetamideYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 600 mg (2.38 mmol) 1-Phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2,4-dione in 16 mL DMF is added 2.62 mL (2.62 mmol, 1.1 equiv) of 1M Sodium bis(trimethylsilyl)amide in THF at ambient temperature and stirred 0.5 h. To this solution is added 707 mg (2.62 mmol, 1.1 equiv) 2-Bromo-N-tert-butyl-N-phenyl-acetamide, prepared as in Part A, in 4 mL DMF and stirred 18 h at ambient temperature. The solvent is removed in vacuo and the residue taken into 50 mL EtOAc, washed successively with H2O (30 mL), 1N HCl (30 mL), satd. NaHCO3 (30 mL), and brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo to a brown oil. The crude product is purified by flash chromatography on 40 g silica gel eluted successively with EtOAc/Hexanes (2:3, 500 mL), (1:1, 750 mL). Appropriate fractions were combined and concentrated in vacuo to give 748 mg (1.69 mmol) of N-tert-Butyl-2-(2,4-dioxo-5-phenyl-2,3,4,5,-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-phenyl-acetamide as a white foam: 1H NMR (CDCl3, 300 MHz) δ7.45-7.21 (m, 12H), 7.08 (t, 1H), 6.90 (m, 1H), 4.30 (d, 1H, J=16.4), 3.85 (d, 1H, J=16.6), 3.59 (d, 1H, J=12.0), 3.49 (d, 1H, J=11.9), 1.43 (s, 9H); TLC Rf =0.24 (EtOAc/Hexanes, 1:1).

Workup

  1. additionTo this solution is added
  2. customThe solvent is removed in vacuo
  3. washwashed successively with H2O (30 mL), 1N HCl (30 mL)
  4. dry with materialNaHCO3 (30 mL), and brine (30 mL), dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to a brown oil
  7. customThe crude product is purified by flash chromatography on 40 g silica gel
  8. washeluted successively with EtOAc/Hexanes (2:3, 500 mL), (1:1, 750 mL)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4254d212a29946edaf673db7300c3acb
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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