Toluene → HCID 58691214, compound

HRID 1392103Notes

Reaction equation

HRID 1392103 reaction equation
[CH:1]1([N:6]([C@H:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29]C=2)C=C)[C:7](=[O:23])[CH:8]([N:12]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:22])[CH2:9][CH:10]=[CH2:11])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:33]1([CH3:39])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl>[CH:1]1([N:6]2[C@H:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:33]=3)[CH:11]=[CH:10][CH2:9][C@@H:8]([N:12]3[C:20](=[O:21])[C:15]4[C:14](=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:13]3=[O:22])[C:7]2=[O:23])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:1]1([N:6]2[C@H:39]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH:11]=[CH:10][CH2:9][C@H:8]([N:12]3[C:20](=[O:21])[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]3=[O:22])[C:7]2=[O:23])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 1140TolueneHCID 58691208HCID 58691208, compound

Product 2

HCID 58691211HCID 58691211, compoundHCID 58691214HCID 58691214, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 178479819HCID 178479819, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

To a solution of N-cyclopentyl-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-[(1S)-1-phenylprop-2-en-1-yl]pent-4-enamide (330 mg) dissolved in Toluene (30 mL) at 80° C. under N2 was added Grubbs catalyst (2nd generation) (33 mg) and the reaction mixture was stirred at 80° C. for 35 minutes, cooled to RT and concentrated in vacuo. The crude product was directly purified via flash chromatography (gradient—10%, 15% EtOAc/hexanes) to give the title compounds, 2-[(3R,7S)-1-cyclopentyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]-1H-isoindole-1,3(2H)-dione (8d) (182 mg) and 2-[(3S,7S)-1-cyclopentyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]-1H-isoindole-1,3(2H)-dione (8c) (95 mg, combined yield of 90%). (8d) 1H NMR (300 MHz, CDCl3) δ 1.44-1.70 (m, 6H), 1.85-2.04 (m, 3H), 2.36-2.43 (m, 1H), 3.69-3.81 (m, 1H), 5.02-5.15 (m, 2H), 5.18-5.30 (m, 1H), 5.98-6.05 (m, 1H), 6.35-6.42 (m, 1H), 7.19-7.52 (m, 5H), 7.64-7.87 (m, 4H). MS APCI, m/z=401 (M+1), LC/MS, 2.73 min. (8c) 1H NMR (300 MHz, CDCl3) δ 1.14-1.88 (m, 9H), 2.25-2.32 (m, 1H), 3.37-3.48 (m, 1H), 4.01-4.11 (m, 1H), 5.30 (dd, 1H, J=13 Hz, J=4 Hz), 5.52 (d, 1H, J=7 Hz), 6.04-6.11 (m, 1H), 6.43-6.50 (m, 1H), 7.29-7.55 (m, 5H), 7.69-7.90 (m, 4H). MS APCI, m/z=401 (M+1), LC/MS, 2.80.

Workup

  1. temperaturecooled to RT
  2. concentrationconcentrated in vacuo
  3. customThe crude product was directly purified via flash chromatography (gradient—10%, 15% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f4f7dea2dbcb47ddb2a042e53d08acca
Source dataset
uspto-grants-2008_03
Patent number
US07342007B2

Reaction notes

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