O-Phenylenediamine → Ethyl (+/-)-3-[3-[[(2-aminophenyl)amino]carbonyl]prop-1-yl]-5H-dibenzo[a,d]cycloheptene-10-acetate

HRID 613388Notes

Reaction equation

HRID 613388 reaction equation
[C:1]([CH2:4][CH2:5][CH2:6][C:7]1[CH:8]=[CH:9][C:10]2[CH:16]=[C:15]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:14]3[CH:23]=[CH:24][CH:25]=[CH:26][C:13]=3[CH2:12][C:11]=2[CH:27]=1)(O)=[O:2].CN1CCOCC1.ClC(OCC(C)C)=O.[C:43]1([NH2:50])[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[NH2:49]>C1COCC1.O>[NH2:49][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=1[NH:50][C:1]([CH2:4][CH2:5][CH2:6][C:7]1[CH:8]=[CH:9][C:10]2[CH:16]=[C:15]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:14]3[CH:23]=[CH:24][CH:25]=[CH:26][C:13]=3[CH2:12][C:11]=2[CH:27]=1)=[O:2]

Participants

7

Reactant 4

HCID 7243O-PhenylenediamineHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 54111116Ethyl (+/-)-3-[3-carboxy-1-propyl]-5H-dibenzo [a,d]cycloheptene-10-acetate

Product 1

HCID 53849297Ethyl (+/-)-3-[3-[[(2-aminophenyl)amino]carbonyl]prop-1-yl]-5H-dibenzo[a,d]cycloheptene-10-acetateYield 88.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of ethyl (±)-3-[3-carboxy-1-propyl]-5H-dibenzo[a,d]cycloheptene-10-acetate (233.7 mg, 0.64 mmole) in dry THF (6.4 mL) was cooled to 0° C. under argon, and 4-methylmorpholine (0.14 mL, 1.28 mmole) was added. The solution was stirred at 0° C. for several min, then isobutyl chloroformate (0.11 mL, 0.83 mmole) was added dropwise. The cloudy reaction was stirred at 0° C. for 0.5 hr, then a solution of 1,2-phenylenediamine (138 mg, 1.28 mmole) in dry THF (0.6 mL) was added rapidly. The reaction was warmed to RT and stirred for 3 hr, then was diluted with H2O (2 mL) and extracted with EtOAc. Drying (MgSO4), concentration, and silica gel chromatography (3:2 EtOAc/hexanes) gave the title compound (257.6 mg, 88%) as a light yellow foam: TLC (3:2 EtOAc/hexanes) Rf 0.40; 1H NMR (250 MHz, CDCl3) δ 6.90-7.23 (m, 10 H), 6.72-6.80 (m, 2 H), 4.33 (d, J=15.0 Hz, 1 H), 4.10-4.25 (m, 2 H), 3.71-3.91 (m, 4 H), 3.32 (dd, J=15.1, 4.0 Hz, 1 H), 2.95 (dd, J=15.1, 9.5 Hz, 1 H), 2.59-2.72 (m, 3 H), 2.54 (dd, J=15.6,9.5 Hz, 1 H), 2.34 (t, J=7.4 Hz, 2 H), 1.98-2.09 (m, 2 H), 1.27 (t, J=7.1 Hz, 3 H); MS (ES) m/e 457 (M+H)+.

Workup

  1. customThe cloudy reaction
  2. stirringwas stirred at 0° C. for 0.5 hr
  3. temperatureThe reaction was warmed to RT
  4. stirringstirred for 3 hr
  5. extractionextracted with EtOAc
  6. customDrying
  7. concentration(MgSO4), concentration, and silica gel chromatography (3:2 EtOAc/hexanes)

Sources & evidence

ORD record
ord-dfc84531e1444a03b9bc83126904f065
Source dataset
uspto-grants-1999_12
Patent number
US06008213

Reaction notes

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