Allyltrimethylsilane → tert-butyl [7-(hepta-1,6-dien-4-yl)-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl]carbamate

HRID 511492Notes

Reaction equation

HRID 511492 reaction equation
C(O[CH:5]([C:9]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[C:14]2[C:10]=1[CH2:11][N:12]([CH3:27])[C:13]2=[O:26])[CH2:6][CH:7]=[CH2:8])(=O)C.[Br-].[Br-].[Br-].[In+3].[CH2:32]([Si](C)(C)C)[CH:33]=[CH2:34]>C(Cl)Cl>[CH2:8]=[CH:7][CH2:6][CH:5]([C:9]1[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:20])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[C:14]2[C:10]=1[CH2:11][N:12]([CH3:27])[C:13]2=[O:26])[CH2:34][CH:33]=[CH2:32]

Participants

5

Reactant 3

HCID 69808AllyltrimethylsilaneHCID 167051indium(III)bromideHCID 672543181-{7-[(tert-butoxycarbonyl)amino]-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl}but-3-en-1-yl acetate2×

Product 1

HCID 58293015tert-butyl [7-(hepta-1,6-dien-4-yl)-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl]carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-{7-[(tert-butoxycarbonyl)amino]-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl}but-3-en-1-yl acetate (Compound 243E, 895 mg, 2.39 mmol) in DCM (30 mL) were added indium tribromide (85 mg, 0.24 mmol), followed by the addition of allyltrimethylsilane (550 mg, 4.8 mmol) in DCM (0.5 mL). The resulting mixture was refluxed under nitrogen overnight. The solvent was evaporated and the residue was purified by silica gel chromatography (ISCO Combi-flash system, eluting with 10-50% EtOAc/Heptane) to give the desired product as a white solid, 180 mg. The unreacted starting material was recovered and resubjected to the reaction using 2.0 eq. allyltrimethylsilane and 0.2 eq. InBr3. The mixture was refluxed overnight. The solvent was evaporated and the residue was purified by silica gel chromatography (ISCO Combi-flash system, eluting with 10-50% EtOAc/Heptane) to give the desired product as a white solid, 125 mg. Totally 305 mg, 36% yield. 1H NMR (CDCl3): 1.53 (s, 9H), 2.34-2.47 (m, 4H), 2.67 (m, 1H), 3.16 (s, 3H), 4.27 (s, 2H), 4.92-4.99 (m, 4H), 5.55-5.64 (m, 2H), 7.29 (d, J=8.6 Hz, 1H), 8.16 (d, J=8.6 Hz, 1H), 9.52 (br s, 1H). MS (ES+): m/z=379.13 [MNa+]. HPLC: tR=4.83 min (ZQ3, polar—5 min).

Workup

  1. temperatureThe resulting mixture was refluxed under nitrogen overnight
  2. customThe solvent was evaporated
  3. customthe residue was purified by silica gel chromatography (ISCO Combi-flash system, eluting with 10-50% EtOAc/Heptane)

Sources & evidence

ORD record
ord-ee33992c6e21426ba5cc15fff6cd7a77
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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