Propanedioyl dichloride → tert-butyl (2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl)acetate

HRID 1375354Notes

Reaction equation

HRID 1375354 reaction equation
[NH:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23](Cl)(=[O:28])[CH2:24][C:25](Cl)=[O:26]>C1COCC1>[O:26]=[C:25]1[N:14]([CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:1]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:23](=[O:28])[CH2:24]1

Participants

4

Reactant 2

HCID 74269Propanedioyl dichlorideHCID 69425039tert-butyl N-(2-anilinophenyl)glycinate

Product 1

HCID 86602389tert-butyl (2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl)acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To 100 mL of THF at 0° C. was added dropwise over 20 min simultaneously a solution of the tert-butyl N-(2-anilinophenyl)glycinate (9.5 g, 31.8 mM) in 100 mL of THF and solution of malonyl dichloride (5.38 mL, 38.21 mM) in 100 mL of THF. The resulting solution was stirred at RT for 20 h and the solvent removed in vacuo. The resultant material was purified by silica gel flash column chromatography using hexanes/EtOAc 6/14 and the combined filtrates evaporated in vacuo to give 10.2 g of product. 1H NMR (DMSO-d6) 1.40 (s, 9H), 3.19 (d, J=12 Hz, 1H), 3.69 (d, J=12 Hz, 1H), 4.55 (d, J=17 Hz, 1H), 4.71 (d, J=17 Hz, 1H), 6.89 (d, J=8 Hz, 1H), 7.20 (t, J=8 Hz, 1H), 7.33 (m, 4H), 7.46 (m, 3H).

Workup

  1. customthe solvent removed in vacuo
  2. customThe resultant material was purified by silica gel flash column chromatography
  3. customthe combined filtrates evaporated in vacuo

Sources & evidence

ORD record
ord-678afc13401744dc8b7cabd8de2e9a1e
Source dataset
uspto-grants-2007_01
Patent number
US07169773B2

Reaction notes

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