Phthalimide → 1-((1,3-Dioxoisoindolin-2-yl)methyl)-cyclopropanecarbonitrile

HRID 885714Notes

Reaction equation

HRID 885714 reaction equation
O[CH2:2][C:3]1([C:6]#[N:7])[CH2:5][CH2:4]1.[C:8]1(=[O:18])[NH:12][C:11](=[O:13])[C:10]2=[CH:14][CH:15]=[CH:16][CH:17]=[C:9]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[O:13]=[C:11]1[C:10]2[C:9](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:8](=[O:18])[N:12]1[CH2:2][C:3]1([C:6]#[N:7])[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 220282071-(Hydroxymethyl)cyclopropane-1-carbonitrile

Product 1

HCID 698106701-((1,3-Dioxoisoindolin-2-yl)methyl)-cyclopropanecarbonitrileYield 68.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(hydroxymethyl)-cyclopropanecarbonitrile (5.52 g, 56.8 mmol), phthalimide (9.20 g, 62.5 mmol), and triphenylphosphine (16.4 g, 62.5 mmol) in THF (550 mL) was treated with DEAD (9.90 mL, 62.5 mmol) and stirred at room temperature for 17 hours. The reaction mixture was then concentrated and the resulting solids were triturated in diethyl ether (150 mL), and collected by filtration. Purification by flash chromatography (SiO2, 0-20% EtOAc in DCM) afforded 1-((1,3-dioxoisoindolin-2-yl)methyl)-cyclopropanecarbonitrile (8.8 g, 38.8 mmol, 68%) as a white solid: LCMS(m/z) 227.0 (MH+), tR=0.66 minute; 1H NMR (300 MHz, CDCl3) δ 7.90 (dd, J=5.4, 3.1 Hz, 2H), 7.77 (dd, J=5.4, 3.1 Hz, 2H), 3.81 (s, 2H), 1.30-1.44 (m, 2H), 1.28 (d, J=3.8 Hz, 2H).

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. customthe resulting solids were triturated in diethyl ether (150 mL)
  3. filtrationcollected by filtration
  4. customPurification by flash chromatography (SiO2, 0-20% EtOAc in DCM)

Sources & evidence

ORD record
ord-2c041affd6df4706a5059a71f8277220
Source dataset
uspto-grants-2012_08
Patent number
US08242260B2

Reaction notes

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