3-Aminocyclohex-2-en-1-one → Tert-butyl(1-(4-(5-oxo-3-phenyl-5,6,7,8-tetrahydroquinolin-2-yl)phenyl)cyclobutyl)carbamate

HRID 1509069Notes

Reaction equation

HRID 1509069 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18](=O)[C:19]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20]N(C)C)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH2:32][C:33]1[CH2:38][CH2:37][CH2:36][C:35](=[O:39])[CH:34]=1>C(O)(=O)C>[C:1]([O:5][C:6](=[O:31])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:20][C:34]4[C:35](=[O:39])[CH2:36][CH2:37][CH2:38][C:33]=4[N:32]=3)=[CH:16][CH:17]=2)[CH2:9][CH2:10][CH2:11]1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 788923-Aminocyclohex-2-en-1-oneHCID 66719111HCID 66719111, compound

Product 1

HCID 123451908Tert-butyl(1-(4-(5-oxo-3-phenyl-5,6,7,8-tetrahydroquinolin-2-yl)phenyl)cyclobutyl)carbamateYield 37.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

To acetic acid (120 mL) was added molecular sieves (5 Å, 1.50 g), tert-butyl(1-(4-(3-(dimethylamino)-2-phenylacryloyl)phenyl)cyclobutyl)carbamate (8.00 g, 19.0 mmol) and 3-amino-2-cyclohexene-1-one (3.20 g, 28.8 mmol). The reaction mixture was heated to 100° C. under a nitrogen atmosphere for 2 hours. The mixture was allowed to cool to room temperature and concentrated under reduced pressure. The residue was partitioned between water (160 mL) and dichloromethane (160 mL) and decanted from the molecular sieves. The layers were separated and the aqueous phase extracted into dichloromethane (2×160 mL). The combined organic phases were washed with saturated NaHCO3 solution (2×160 mL), brine (160 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure to give a yellow/brown solid. This was purified by Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 90:10 to 20:80) to give the desired product as a yellow solid (3.30 g, 37% yield). 1H-NMR (500 MHz, CDCl3) δ 8.30 (1H, s), 7.37 (2H, d), 7.30 (2H, d), 7.24-7.27 (3H, m), 7.15-7.20 (2H, m), 5.01 (1H, br s), 3.26 (2H, t), 2.75 (2H, t), 2.42-2.55 (4H, m), 2.26 (2H, p), 2.00-2.10 (1H, m), 1.73-1.85 (1H, m), 1.12-1.44 (9H, br m). LCMS (Method A) RT=7.54 min, M+H+=469.15.

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was partitioned between water (160 mL) and dichloromethane (160 mL)
  4. customdecanted from the molecular sieves
  5. customThe layers were separated
  6. extractionthe aqueous phase extracted into dichloromethane (2×160 mL)
  7. washThe combined organic phases were washed with saturated NaHCO3 solution (2×160 mL), brine (160 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness under reduced pressure
  11. customto give a yellow/brown solid
  12. customThis was purified by Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 90:10 to 20:80)

Sources & evidence

ORD record
ord-f53c764a5a07444485dcbb82700ce2ed
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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