Cyclohexene oxide → HCID 131734330, compound

HRID 1504541Notes

Reaction equation

HRID 1504541 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19].[CH:23]12[O:29][CH:24]1[CH2:25][CH2:26][CH2:27][CH2:28]2>C1(C)C=CC=CC=1>[CH2:9]([S:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]2[OH:29])=[C:3](/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:4]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 9246Cyclohexene oxide2×HCID 117740420(E)-Ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate

Product 1

HCID 131734330HCID 131734330, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A 100-mL pressure vessel was charged with (E)-ethyl 3-(2-amino-5-(benzylthio) phenyl)acrylate (3 g, 9.57 mmol), toluene (31.9 ml), cyclohexene oxide (2.91 ml, 28.7 mmol), and activated Al2O3 (24 g, 9.57 mmol) (dried at 150° C. for 16 h). The reaction vessel was sealed with a Teflon cap and the yellow reaction mixture was warmed to 80° C. After 16 h, additional cyclohexene oxide (2.91 ml, 28.7 mmol) and activated Al2O3(10 g, 3.98 mmol) was added and the reaction vessel was sealed with a Teflon cap and warmed to 80° C. After 48 h, the reaction mixture was allowed to cool to RT then filtered through a fritted funnel and the pad of Al2O3 was eluted with EtOAc (2×100 mL). The filtrate was concentrated under reduced pressure to furnish a yellow residue which was purified by flash column chromatography (100-g Biotage column, eluent: gradient, 0 to 50% EtOAc in heptane) to afford (±)-(E)-ethyl 3-(5-(benzylthio)-2-((2-hydroxycyclohexyl)amino) phenyl)acrylate (3.5 g, 8.50 mmol, 89% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ=7.84 (d, J=15.7 Hz, 1H), 7.37 (d, J=2.3 Hz, 1H), 7.31-7.18 (m, 6H), 7.14 (dd, J=2.2, 8.7 Hz, 1H), 6.65 (d, J=8.9 Hz, 1H), 6.27 (d, J=15.5 Hz, 1H), 5.48 (d, J=6.8 Hz, 1H), 4.75 (d, J=5.0 Hz, 1H), 4.03 (s, 1H), 3.52-3.39 (m, 1H), 3.20-3.11 (m, 1H), 3.07 (d, J=8.9 Hz, 1H), 1.90 (d, J=9.7 Hz, 1H), 1.80 (d, J=2.5 Hz, 1H), 1.70-1.50 (m, 2H), 1.21-1.05 (m, 2H). m/z (ESI) 412.0 (M+H)+.

Workup

  1. customcap
  2. customcap
  3. temperaturewarmed to 80° C
  4. waitAfter 48 h
  5. temperatureto cool to RT
  6. filtrationthen filtered through a fritted funnel
  7. washthe pad of Al2O3 was eluted with EtOAc (2×100 mL)
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customto furnish a yellow residue which
  10. customwas purified by flash column chromatography (100-g Biotage column, eluent: gradient, 0 to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-013d3ca4825e4e62aff5714521d5273b
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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