Ozone → 2-(4-Amino-3-oxo-1,3,4,5-tetrahydro-benzo[c]azepin-2-yl)-4-methyl-valeric acid, tert-butyl ester

HRID 1264545Notes

Reaction equation

HRID 1264545 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=O)[N:3]1[CH:12]([CH2:22][C:23]1[CH:28]=CC=C[C:24]=1C=C)[C:13]([O:15]CC[Si](C)(C)C)=[O:14].O=[O+][O-]>C(Cl)Cl.CO>[NH2:3][CH:2]1[C:2](=[O:1])[N:3]([CH:12]([CH2:22][CH:23]([CH3:24])[CH3:28])[C:13]([O:15][C:23]([CH3:28])([CH3:24])[CH3:22])=[O:14])[CH2:4][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=2[CH2:10]1

Participants

5

Reactant 2

HCID 24823OzoneHCID 541575632-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-vinyl-phenyl)-propionic acid, 2-trimethylsilanyl-ethyl ester

Product 1

HCID 865855102-(4-Amino-3-oxo-1,3,4,5-tetrahydro-benzo[c]azepin-2-yl)-4-methyl-valeric acid, tert-butyl esterYield 247.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Dissolve 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-vinyl-phenyl)-propionic acid, 2-trimethylsilanyl-ethyl ester (2.61 g, 6.19 mmol) in methylene chloride (70 mL) and methanol (75 mL). Cool to −78° C. and treat with ozone until a blue color persists. Purge with nitrogen and add dimethylsulfide (7 mL) and pyridine (0.35 mL). Allow to warm to room temperature gradually overnight. Partition between methylene chloride (100 mL) and water (40 mL). Extract the aqueous with methylene chloride (50 mL), dry (Na2SO4) and purify by silica gel chromatography (2.5:1 hexane/ethyl acetate) to give the title compound as a colorless viscous oil (2.65 g, 100%). Step h: 2-(2-(2-(1,3,-Dioxo-1,3,dihydro-isoindol-2-yl)-2-(2-trimethylsilanyl-ethoxycarbonyl)-ethyl)-benzylamino)-4-methyl-valeric acid, tert-butyl ester.

Workup

  1. customPurge with nitrogen
  2. additionadd dimethylsulfide (7 mL) and pyridine (0.35 mL)
  3. temperatureAllow to warm to room temperature gradually overnight
  4. customPartition between methylene chloride (100 mL) and water (40 mL)
  5. extractionExtract the aqueous with methylene chloride (50 mL)
  6. dry with materialdry (Na2SO4)
  7. custompurify by silica gel chromatography (2.5:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-b3c5790cb36d40b598d78fd4e7c7d738
Source dataset
uspto-grants-2003_04
Patent number
US06544980B2

Reaction notes

Loading…