Triethylamine → HCID 178525702, compound

HRID 1893365Notes

Reaction equation

HRID 1893365 reaction equation
Cl[C:2](=[N:13][OH:14])[C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([O:11]C)=[O:10])[CH2:5][CH2:4]1.[C:15]1(N2CCOCC2)[CH2:19][CH2:18][CH2:17][CH:16]=1.C(N(CC)CC)C>ClCCl>[O:14]1[C:16]2[CH2:17][CH2:18][CH2:19][C:15]=2[C:2]([C@H:3]2[CH2:8][CH2:7][C@H:6]([C:9]([OH:11])=[O:10])[CH2:5][CH2:4]2)=[N:13]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 702941-MorpholinocyclopenteneHCID 178501086HCID 178501086, compound

Product 1

HCID 178525702HCID 178525702, compoundYield 6.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of trans-methyl 4-(chloro(hydroxyimino)methyl)cyclohexanecarboxylate (0.900 g, 4.10 mmol) and 4-cyclopentenylmorpholine (1.23 ml, 8.19 mmol) in dichloromethane (21 ml) was added triethylamine (0.714 ml, 5.12 mmol) at 0-5° C. The reaction mixture was allowed to warm to room temperature and stirred for 20 h. The solvent was evaporated. The residue was redissolved in 6 M aqueous hydrogen chloride solution (20.5 ml) and stirred at reflux for 4 h. After cooling to room temperature the reaction mixture was poured on ice, basified with 2 M aqueous sodium hydroxide solution (80 ml) and washed with two 50-ml portions of ethyl acetate. The combined organic layers were extracted with two 50-ml portions of 1 M aqueous sodium hydroxide solution. The combined aqueous layers were acidified to pH 2-3 by addition of concentrated hydrochloric acid and extracted with three 100-ml portions of ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was triturated in tert-butyl methyl ether (50 ml). The precipitate was removed by filtration. The filtrate was concentrated in vacuo. The residue was purified by flash chromatography with n-heptane/ethyl acetate as eluent to give the title compound (0.060 g, 6%) as off-white solid. MS m/e: 234 ([M−H]−)

Workup

  1. customThe solvent was evaporated
  2. dissolutionThe residue was redissolved in 6 M aqueous hydrogen chloride solution (20.5 ml)
  3. stirringstirred
  4. temperatureat reflux for 4 h
  5. temperatureAfter cooling to room temperature the reaction mixture
  6. additionwas poured on ice
  7. washwashed with two 50-ml portions of ethyl acetate
  8. extractionThe combined organic layers were extracted with two 50-ml portions of 1 M aqueous sodium hydroxide solution
  9. additionThe combined aqueous layers were acidified to pH 2-3 by addition of concentrated hydrochloric acid
  10. extractionextracted with three 100-ml portions of ethyl acetate
  11. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  12. concentrationconcentrated in vacuo
  13. customThe residue was triturated in tert-butyl methyl ether (50 ml)
  14. customThe precipitate was removed by filtration
  15. concentrationThe filtrate was concentrated in vacuo
  16. customThe residue was purified by flash chromatography with n-heptane/ethyl acetate as eluent

Sources & evidence

ORD record
ord-2b57d47f60d24cf9872fbc4784f7de2d
Source dataset
uspto-grants-2013_08
Patent number
US08513238B2

Reaction notes

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