Hydrazine hydrate (1:1) → HCID 178514430, compound

HRID 1516166Notes

Reaction equation

HRID 1516166 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=2)[CH2:7][CH2:6]1)=O.O.[NH2:23][NH2:24]>CO.O1CCOCC1>[C:12]1([O:11][C@H:8]2[CH2:9][CH2:10][C@H:5]([C:3]([NH:23][NH2:24])=[O:2])[CH2:6][CH2:7]2)[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)2×HCID 178501255HCID 178501255, compound

Product 1

HCID 178514430HCID 178514430, compoundYield 93.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of trans-4-(naphthalen-1-yloxy)-cyclohexanecarboxylic acid methyl ester (0.130 g, 0.457 mmol) and hydrazine hydrate (0.022 ml, 0.45 mmol) in methanol (0.5 ml) was heated at 80° C. for 16 h. After cooling to room temperature the reaction mixture was partitioned between ethyl acetate (50 ml) and 1 M aqueous sodium hydroxide solution (50 ml). The organic layer was separated. The aqueous layer was extracted with two 50-ml portions of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo to give a 3:1 mixture of the crude title compound and starting material. This mixture (0.12 g) and hydrazine hydrate (0.022 ml, 0.45 mmol) were dissolved in 1,4-dioxane (0.4 ml) and heated at reflux for 18 h. After cooling to room temperature the reaction mixture was partitioned between ethyl acetate (50 ml) and 1 M aqueous sodium hydroxide solution (50 ml). The organic layer was separated. The aqueous layer was extracted with two 50-ml portions of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo to give the crude title compound (0.120 g, 83%) as yellow solid with a purity of 90%, which was used in the next step without further purification. MS m/e: 285 (M+H+)

Workup

  1. temperatureAfter cooling to room temperature the reaction mixture
  2. customwas partitioned between ethyl acetate (50 ml) and 1 M aqueous sodium hydroxide solution (50 ml)
  3. customThe organic layer was separated
  4. extractionThe aqueous layer was extracted with two 50-ml portions of ethyl acetate
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give
  8. additiona 3:1 mixture of the crude title compound
  9. temperatureheated
  10. temperatureat reflux for 18 h
  11. temperatureAfter cooling to room temperature the reaction mixture
  12. customwas partitioned between ethyl acetate (50 ml) and 1 M aqueous sodium hydroxide solution (50 ml)
  13. customThe organic layer was separated
  14. extractionThe aqueous layer was extracted with two 50-ml portions of ethyl acetate
  15. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-84c39d0c2f95472790dbf1d917de943c
Source dataset
uspto-grants-2012_07
Patent number
US08227458B2

Reaction notes

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