Acrylonitrile → (+/-)-tert-butyl (1R,5S,65)-6-(2-cyanoethoxy)-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamate

HRID 705291Notes

Reaction equation

HRID 705291 reaction equation
[OH:1][C@@H:2]1[C@H:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:6]=[C:5]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][C:17]=2[N+:22]([O-:24])=[O:23])[CH2:4][C@@H:3]1[CH3:25].[C:26](#[N:29])[CH:27]=[CH2:28].C(=O)([O-])[O-].[Cs+].[Cs+].C([O-])(O)=O.[Na+]>CC(O)(C)C.O>[C:26]([CH2:27][CH2:28][O:1][C@@H:2]1[C@H:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14])[CH:6]=[C:5]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][C:17]=2[N+:22]([O-:24])=[O:23])[CH2:4][C@@H:3]1[CH3:25])#[N:29]

Participants

7

Reactant 4

HCID 7855AcrylonitrileHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 86705242(+/-)-Tert-butyl (1R,5S,6S)-6-hydroxy-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamate

Product 1

HCID 86705253(+/-)-tert-butyl (1R,5S,65)-6-(2-cyanoethoxy)-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamateYield 94%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
35 °C

Procedure

A mixture of (+/−)-Tert-butyl (1R,5S,65)-6-hydroxy-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamate (1.0 equiv.), acrylonitrile (30.0 equiv.) and CESIUM CARBONATE (1.2 equiv.) in t-BuOH (0.57 M) was stirred at 35° C. for 3 hrs. The reaction was cooled to room temperature, followed by the addition of NaHCO3(aq) and water. The mixture was extracted with EtOAc and the combined organics were dried over MgSO4, filtered, and concentrated. The sample was purified by ISCO SiO2 chromatography to yield (+/−)-tert-butyl (1R,5S,6S)-6-(2-cyanoethoxy)-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamate in 94% yield. LC/MS (m/z)=403.3 (MH+), Rt=0.92 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.13 (d, J=6.46 Hz, 3 H), 1.46 (s, 9 H), 1.99-2.18 (m, 2 H), 2.20-2.36 (m, 1 H), 2.65 (t, J=6.06 Hz, 2 H), 3.68 (br. s., 1 H), 3.88 (t, J=5.99 Hz, 2 H), 4.51 (br. s., 1 H), 4.99 (d, J=9.15 Hz, 1 H), 5.39 (br. s., 1 H), 7.25 (d, J=4.99 Hz, 1 H), 8.73 (d, J=4.94 Hz, 1 H), 9.10 (s, 1 H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionThe mixture was extracted with EtOAc
  3. dry with materialthe combined organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe sample was purified by ISCO SiO2 chromatography

Sources & evidence

ORD record
ord-24fde94673cc43d991f9d235db9a9f2e
Source dataset
uspto-grants-2015_11
Patent number
US09173883B2

Reaction notes

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