Toluene → HCID 67635347, compound

HRID 1938149Notes

Reaction equation

HRID 1938149 reaction equation
[C:1]1(=[O:19])[N:5]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]C(O)=O)[C:4](=[O:14])[C:3]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:2]12.S(Cl)(Cl)=[O:21].[CH:24]([NH:27][CH:28](C)C)([CH3:26])[CH3:25].[C:31]1([CH3:37])[CH:36]=CC=CC=1>CN(C=O)C.C(Cl)Cl>[CH:24]([N:27]([CH:31]([CH3:36])[CH3:37])[C:28](=[O:21])[CH:6]([N:5]1[C:1](=[O:19])[C:2]2=[CH:18][CH:17]=[CH:16][CH:15]=[C:3]2[C:4]1=[O:14])[CH2:7][CH2:8][CH2:9][CH3:10])([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 1140TolueneHCID 7912DiisopropylamineHCID 24386Thionyl ChlorideHCID 781851,3-Dihydro-1,3-dioxo-2H-isoindole-2-hexanoic acid

Product 1

HCID 67635347HCID 67635347, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-phthalimidohexanoic acid (7.83 g, 30 mmol) in 100 mL toluene and 1 mL DMF was added thionyl chloride (7.2 mL, 160 mmol) and the mixture heated at 100° C. for 1 h. After evaporation the residual acid chloride was dissolved in 25 mL methylene chloride and added to diisopropylamine (7.0 g, 70 mmol) in 100 mL methylene chloride at 0-10 C. The mixture was stirred at rt for 2 H, the solvent removed, the residue taken up in ether and extracted with 2N HCl. The organic solvent was removed and the residue recrystallized from diisopropylether/hexane (3:2). Yield 70% of phthalimidohexanoic acid diisopropylamide. Mp 85°-86° C. This amide (1.03 g, 3 mmol) and hydrazinhydrate (250 mg, 5.3 mmol) were heated in ethanol at 80 C. for 6 h. The mixture was cooled and filtered, the solvent removed and the residue taken up in H2O and ethyl acetate. The organic phase yielded 440 mg (70%) of 6-aminohexanoic acid diisopropylamide. This compound (440 mg, 2.0 mmol) was reacted with aceton (240 mg, 6 mmol) and sodium cyanoborohydride (226 mg, 3 mmol) in methanol (pH adjusted to 5-6 with acetic acid) at rt for 5 h. 2 mL 2M HCl was added, the solvent removed and the residue taken up in ether after alkalisation. Yield 400 mg (78%) of 6-isopropylaminohexanoic acid diisopropylamide. This secondary amide (400 mg, 1.6 mmol), 2-methoxyphenethyl bromide (from 2-methoxyphenethyl-alcohol and PBr3, 516 mg, 2.4 mmol), and potassium carbonate (330 mg, 2.4 mmol) in 20 mL DMF were heated for 20 h. The solvent was removed and the residue purified by flash chromatography in aceton. Yield 180 mg (30%) of the title compound.

Workup

  1. customAfter evaporation the residual acid chloride
  2. dissolutionwas dissolved in 25 mL methylene chloride
  3. customthe solvent removed
  4. extractionextracted with 2N HCl
  5. customThe organic solvent was removed
  6. customthe residue recrystallized from diisopropylether/hexane (3:2)

Sources & evidence

ORD record
ord-1b5ccc4605a244148e12d52e2cf9d80d
Source dataset
uspto-grants-1997_12
Patent number
US05693630

Reaction notes

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