Triphenylphosphine → 5-Chloro-N-[1,3-dioxo-2-(4-piperidinylmethyl)-2,3-dihydro-1H-isoindol-4-yl]-2-thiophenecarboxamide

HRID 1455679Notes

Reaction equation

HRID 1455679 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[Cl:13][C:14]1[S:18][C:17]([C:19]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:23]=2[C:24](=[O:32])[NH:25][C:26]3=[O:31])=[O:20])=[CH:16][CH:15]=1.O[CH2:34][CH:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[Cl:13][C:14]1[S:18][C:17]([C:19]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:23]=2[C:24](=[O:32])[N:25]([CH2:34][CH:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[C:26]3=[O:31])=[O:20])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 4207714-PiperidinemethanolHCID 41357405-Chloro-N-(1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)thiophene-2-carboxamide

Product 1

HCID 120748925-Chloro-N-[1,3-dioxo-2-(4-piperidinylmethyl)-2,3-dihydro-1H-isoindol-4-yl]-2-thiophenecarboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

At room temperature, 0.43 ml (2.73 mmol) of diethyl azodicarboxylate (DEAD) is added dropwise to a suspension of 670 mg (2.18 mmol) of 5-chloro-N-(1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)-2-thiophenecarboxamide, 314 mg (2.73 mmol) of 4-hydroxymethylpiperidine and 716 mg (2.73 mmol) of triphenylphosphine in 8.7 ml of absolute THF. After 2 h at room temperature, the mixture is concentrated and the residue is separated by chromatography on silica gel (gradient: from dichloromethane/methanol 95:5 to dichloromethane/methanol/triethylamine 9:1:0.1). Yield: 430 mg (41.5% of theory); MS (ESI): m/z (%)=404 (M+H, 60), 145 (100); LC-MS (Method 4): rt (%) =3.02 (84).

Workup

  1. concentrationthe mixture is concentrated
  2. customthe residue is separated by chromatography on silica gel (gradient: from dichloromethane/methanol 95:5 to dichloromethane/methanol/triethylamine 9:1:0.1)
  3. customrt (%) =3.02 (84)

Sources & evidence

ORD record
ord-4a27b27483b543599ab2b6fef03ca0a6
Source dataset
uspto-grants-2009_01
Patent number
US07482472B2

Reaction notes

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