1-Butanol → 2-[(2S)-2-(5-bromo-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-3-cyclohexylpropyl]-1H-isoindole-1,3(2H)-dione

HRID 340004Notes

Reaction equation

HRID 340004 reaction equation
[NH2:1][C@@H:2]([CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[CH2:3][N:4]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]1=[O:14].[Br:22][C:23]1[CH:32]=[CH:31][C:26]([C:27](OC)=[O:28])=[C:25]([CH2:33]Br)[CH:24]=1.C(N(CC)C(C)C)(C)C.C(O)CCC>>[Br:22][C:23]1[CH:24]=[C:25]2[C:26](=[CH:31][CH:32]=1)[C:27](=[O:28])[N:1]([C@@H:2]([CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[CH2:3][N:4]1[C:5](=[O:14])[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:12]1=[O:13])[CH2:33]2

Participants

5

Reactant 4

HCID 2631-ButanolHCID 81531DiisopropylethylamineHCID 22031079Methyl 4-bromo-2-(bromomethyl)benzoateHCID 670661172-[(2S)-2-amino-3-cyclohexylpropyl]-1H-isoindole-1,3(2H)-dione

Product 1

HCID 866814912-[(2S)-2-(5-bromo-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-3-cyclohexylpropyl]-1H-isoindole-1,3(2H)-dioneYield 54%

Conditions

Temperature
140 °C

Procedure

A mixture of 2-[(2S)-2-amino-3-cyclohexylpropyl]-1H-isoindole-1,3(2H)-dione (914.3 mg, 3.193 mmol), methyl 4-bromo-2-(bromomethyl)benzoate (960.0 mg, 3.117 mmol) and N,N-diisopropylethylamine (0.6 mL, 3 mmol) in 1-butanol (4 mL, 40 mmol) was stirred at 140° C. for 2 h under microwave irradiation. Direct purification by combi-flash chromatography afforded 810 mg (54% yield) of the desired product. LC-MS found: 481.1 (M+H)+.

Workup

  1. customDirect purification by combi-flash chromatography

Sources & evidence

ORD record
ord-305bc0f08af84656b4aa8a890334062b
Source dataset
uspto-grants-2014_11
Patent number
US08895571B2

Reaction notes

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