Pyridine → HCID 58458977, compound

HRID 2387760Notes

Reaction equation

HRID 2387760 reaction equation
Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[O:3].N1C=CC=CC=1.[CH:20]1([CH2:26][C@H:27]([OH:36])[C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[O:29])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>O1CCOCC1>[C:2](=[O:3])([O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:11]([O-:13])=[O:12])=[CH:9][CH:10]=1)[O:36][C@H:27]([C:28]([N:30]1[CH2:31][CH2:32][O:33][CH2:34][CH2:35]1)=[O:29])[CH2:26][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 821294-Nitrophenyl chloroformateHCID 59949122HCID 59949122, compound

Product 1

HCID 58458977HCID 58458977, compoundYield 73.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
70 °C

Procedure

A solution of 4-nitrophenyl chloroformate (20.55 g, 102 mmol) in dioxane (150 mL) is treated with pyridine (50 mL) resulting in a suspension. This material is heated to 70° C. and a solution of 3 (12.30 g, 51.0 mmol) in dioxane (50 mL) is added via pressure equalizing dropping funnel over ˜5 minutes. After stirring for an additional 5 minutes, the reaction is allowed to cool to room temperature and the solvent is removed by rotary evaporation. The resulting mass is partitioned between ethyl acetate and water. The organic layer is collected and the aqueous phase is extracted once more with ethyl acetate and discarded. The combined organics are dried over MgSO4 and the solvent is removed. The resulting solid is dissolved in a minimal amount of hot dichloroethane and treated with dichloromethane. The mixture is then kept in a −4° C. refrigerator overnight and filtered. The mother liquor is concentrated and purified over 330 g of silica gel using a gradient of 0-100% ethyl acetate in hexane to afford 15.2 g (73% yield) of (S)-2-cyclohexyl-1-(morpholine-4-carbonyl)ethyl 4-nitro-phenyl carbonate (4) as a slightly yellow oil; 1H NMR (CDCl3, 400 MHz) δ 0.97-1.08 (m, 2H), 1.09-1.36 (m, 3H), 1.48-4.62 (m, 2H), 1.65-1.68 (m, 4H), 1.82-1.97 (m, 2H), 3.41-3.60 (m, 3H), 3.64-3.80 (m, 5H), 5.29-5.36 (m, 1H), 7.38-7.44 (m, 2H), 8.24-8.30 (m, 2H); HPLC-MS calculated for C20H26N2O7 (M+H+) 407.2, found 407.4.

Workup

  1. customresulting in a suspension
  2. customover ˜5 minutes
  3. temperatureto cool to room temperature
  4. customthe solvent is removed by rotary evaporation
  5. customThe resulting mass is partitioned between ethyl acetate and water
  6. customThe organic layer is collected
  7. extractionthe aqueous phase is extracted once more with ethyl acetate
  8. dry with materialThe combined organics are dried over MgSO4
  9. customthe solvent is removed
  10. dissolutionThe resulting solid is dissolved in a minimal amount of hot dichloroethane
  11. additiontreated with dichloromethane
  12. customis then kept in a −4° C.
  13. customrefrigerator overnight
  14. filtrationfiltered
  15. concentrationThe mother liquor is concentrated
  16. custompurified over 330 g of silica gel using a gradient of 0-100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-63f0cf1fdc4a4a37ba0e8d47fdafdc41
Source dataset
uspto-grants-2012_09
Patent number
US08268996B2

Reaction notes

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