Phthalic Anhydride → tert-butyl(cyclopropylmethyl){trans-2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]cyclopropyl}carbamate

HRID 922550Notes

Reaction equation

HRID 922550 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[N:11]([CH2:19][CH:20]2[CH2:22][CH2:21]2)[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:30]1(=O)[O:35][C:33](=[O:34])[C:32]2=[CH:36][CH:37]=[CH:38][CH:39]=[C:31]12>C1COCC1>[C:14]([O:13][C:12](=[O:18])[N:11]([CH2:19][CH:20]1[CH2:22][CH2:21]1)[C@@H:9]1[CH2:10][C@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([N:1]2[C:33](=[O:34])[C:32]3[C:31](=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:30]2=[O:35])=[CH:3][CH:4]=1)([CH3:17])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 6811Phthalic AnhydrideHCID 8471TriethylamineHCID 86729891Tert-butyl [trans-2-(4-aminophenyl)cyclopropyl](cyclopropylmethyl)carbamate

Product 1

HCID 86729920tert-butyl(cyclopropylmethyl){trans-2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]cyclopropyl}carbamateYield 99.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl [trans-2-(4-aminophenyl)cyclopropyl](cyclopropylmethyl)carbamate (177.9 mg) and triethylamine (98 μL) in THF (2.94 mL) was added phthalic anhydride (105 mg). The mixture was stirred at room temperature overnight and the solvent was evaporated under reduced pressure. The residue was dissolved in acetic anhydride (3 mL), and the mixture was stirred at 80° C. for 5 hr. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (252.7 mg).

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. dissolutionThe residue was dissolved in acetic anhydride (3 mL)
  3. stirringthe mixture was stirred at 80° C. for 5 hr
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-34f35312c6dc446ba1fa330059b0230f
Source dataset
uspto-grants-2016_03
Patent number
US09278931B2

Reaction notes

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