Hydrochloric Acid → 2-[4-(3,4-Dichloro-benzyl)-morpholin-2-ylmethyl]-isoindole-1,3-dione

HRID 227458

Reaction equation

HRID 227458 reaction equation
[O:1]1[CH2:3][CH:2]1[CH2:4][N:5]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:15].[Cl:16][C:17]1[CH:18]=[C:19]([CH:25]=[CH:26][C:27]=1[Cl:28])[CH2:20][NH:21][CH2:22]CO.[C:29]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.Cl>O1CCCC1.C(OCC)(=O)C>[Cl:16][C:17]1[CH:18]=[C:19]([CH:25]=[CH:26][C:27]=1[Cl:28])[CH2:20][N:21]1[CH2:29][CH2:3][O:1][CH:2]([CH2:4][N:5]2[C:6](=[O:15])[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:13]2=[O:14])[CH2:22]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 21601N-(2,3-Epoxypropyl)phthalimideHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2605252-[[(3,4-Dichlorophenyl)methyl]amino]ethanol

Product 1

HCID 219628802-[4-(3,4-Dichloro-benzyl)-morpholin-2-ylmethyl]-isoindole-1,3-dione

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
66 °C

Procedure

To a solution of 2-(oxiran-2-ylmethyl)-1H-isoindole-1,3(2H)-dione (2 g) in tetrahydrofuran (4 ml) was added 2-[(3,4-dichlorobenzyl)amino]ethanol (2.16 g) with stirring, under a nitrogen atmosphere. The mixture was heated to 66° C. for 22 h, then cooled to 0° C. A further portion of tetrahydrofuran (10 ml) was added, followed by triphenylphosphine (2.88 g). Diisopropyl azodicarboxylate (2.2 g) was then added over 10 min. The mixture was stirred at 0° C. for a further 30 min, and at room temperature for 14 h. To the crude solution was added ethyl acetate (100 ml), then 2M aqueous hydrochloric acid (250 ml). The resulting white precipitate was isolated by filtration, and dried in vacuo to give the title compound as its white crystalline hydrochoride salt (2.01 g). This was partitioned between 8% aqueous sodium bicarbonate (200 ml) and ethyl acetate (50 ml). The organic phase was separated, dried over magnesium sulfate and the solvent evaporated in vacuo to give a solid. Dichloromethane (20 ml) was added to the residue and the solvent again evaporated in vacuo to give the title compound as a white solid (1.1 g).

Workup

  1. temperaturecooled to 0° C
  2. stirringThe mixture was stirred at 0° C. for a further 30 min
  3. customThe resulting white precipitate was isolated by filtration
  4. customdried in vacuo

Sources & evidence

ORD record
ord-dc9beebce29943d5b5dbc95dda33fa07
Source dataset
uspto-grants-2009_07
Patent number
US07560548B2

Linked notes

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