Cesium carbonate → (+/-)-tert-butyl (1R,5S,6S)-5-methyl-6-(2-(methylsulfonyl)ethoxy)-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamate

HRID 705297Notes

Reaction equation

HRID 705297 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].[CH3:26][S:27]([CH:30]=[CH2:31])(=[O:29])=[O:28].C(=O)([O-])[O-].[Cs+].[Cs+].C([O-])(O)=O.[Na+]>CC(O)(C)C.O>[CH3:25][C@@H:3]1[C@H:2]([O:1][CH2:31][CH2:30][S:27]([CH3:26])(=[O:29])=[O:28])[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]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 19354Methyl vinyl sulfoneHCID 516892Sodium BicarbonateHCID 86705242(+/-)-Tert-butyl (1R,5S,6S)-6-hydroxy-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamate

Product 1

HCID 86705262(+/-)-tert-butyl (1R,5S,6S)-5-methyl-6-(2-(methylsulfonyl)ethoxy)-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamateYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
22 °C

Procedure

A mixture of (+/−)-Tert-butyl (1R,5 S,65)-6-hydroxy-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamate (1.0 equiv.), methylsulfonylethene (30.0 equiv.) and CESIUM CARBONATE (1.2 equiv.) in t-BuOH (0.22 M) was stirred at 22° C. for 5 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 chromatography to yield (+/−)-tert-butyl (1R,5S,6S)-5-methyl-6-(2-(methylsulfonyl)ethoxy)-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamate in 84% yield. LC/MS (m/z)=456.2 (MH+), Rt=0.87 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.10 (d, J=6.60 Hz, 3 H), 1.47 (s, 9 H), 1.92-2.16 (m, 2 H), 2.17-2.32 (m, 1 H), 2.93-3.00 (m, 1 H), 3.09 (s, 3 H), 3.18 (d, J=14.87 Hz, 1 H), 3.38-3.52 (m, 1 H), 3.63 (d, J=2.40 Hz, 1 H), 3.95-4.06 (m, 1 H), 4.21 (td, J=9.84, 2.42 Hz, 1 H), 4.56 (d, J=7.58 Hz, 1 H), 5.58 (br. s., 1 H), 5.66 (d, J=9.44 Hz, 1 H), 7.20 (d, J=4.99 Hz, 1 H), 8.73 (d, J=4.99 Hz, 1 H), 9.05 (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 chromatography

Sources & evidence

ORD record
ord-060f093d756b4f95a468156b3dbc4b51
Source dataset
uspto-grants-2015_11
Patent number
US09173883B2

Reaction notes

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