Triethylamine → Imipramine

HRID 1901428Notes

Reaction equation

HRID 1901428 reaction equation
[CH:1]1[C:6]([C:7](O)=O)=C[C:4]([C:10]2[C:20]3[CH:21]=[CH:22][C:23](O)=[CH:24][C:19]=3OC3C=2C=CC(C=3)=O)=[C:3]([C:26](O)=O)[CH:2]=1.O[N:30]1C(=O)CC[C:31]1=O.C1(N=C=NC2CCCCC2)CCCCC1.[CH2:52]([N:54]([CH2:57][CH3:58])[CH2:55]C)C>CN(C=O)C>[CH3:52][N:54]([CH2:57][CH2:58][CH2:31][N:30]1[C:26]2[CH:7]=[CH:6][CH:1]=[CH:2][C:3]=2[CH2:4][CH2:10][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]1=2)[CH3:55]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 2725051ST51005980

Product 1

HCID 3696ImipramineYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

6-Carboxyfluorescein (1.00 g, 2.66 mmol) was dissolved in 8 mL DMF, 306 mg (2.66 mmol) of N-hydroxysuccinimide was added, 549 mg (2.66 mmol) of 1,3-dicyclohexylcarbo-diimide was added, and the reaction stirred for 17 hours, under N2, in the dark. The reaction mixture was vacuum filtered, filtrate combined with 7.84 mg (2.65 mmol) of 2-aminoimipramine (4c), 0.56 mL (4.0 mmol) of triethylamine, and 4.0 mL DMF, and reaction allowed to stir 4 days under N2, in the dark. Reaction solvents were removed in vacuo and residue purified on reverse phase C18 semi-preparative (1 mm) TLC plates, eluting with H2O/THF/HOAc (40/60/0.4) followed by preparative HPLC on a Waters mbondapak C18 column (19 mm×150 mm), eluting with H2O/THF/HOAc (35/65/0.4) at a flow rate of 7.0 mL/minute to yield 410 mg (24%) of the desired imipramine tracer (12) as an orange powder; mass spec (FAB) (M+H)+ 654.

Workup

  1. filtrationfiltered
  2. stirringto stir 4 days under N2, in the dark
  3. customReaction solvents
  4. customwere removed in vacuo and residue
  5. custompurified on reverse phase C18 semi-preparative (1 mm) TLC plates
  6. washeluting with H2O/THF/HOAc (40/60/0.4)
  7. washeluting with H2O/THF/HOAc (35/65/0.4) at a flow rate of 7.0 mL/minute

Sources & evidence

ORD record
ord-48e8971862834e53910044b31636b7b2
Source dataset
uspto-grants-1996_11
Patent number
US05578500

Reaction notes

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