Cyclopropanecarbonyl chloride → HCID 54284623, compound

HRID 1384986Notes

Reaction equation

HRID 1384986 reaction equation
[CH:1]1([C:4](Cl)=O)[CH2:3][CH2:2]1.Cl.[CH3:8][C:9]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:10]=1[O:11][CH2:12][C@H:13]1[CH2:18][CH2:17][CH2:16][NH:15][CH2:14]1.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[CH:1]1([CH2:4][N:15]2[CH2:16][CH2:17][CH2:18][C@H:13]([CH2:12][O:11][C:10]3[C:19]([CH3:23])=[CH:20][CH:21]=[CH:22][C:9]=3[CH3:8])[CH2:14]2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 516892Sodium BicarbonateHCID 70238043HCID 70238043, compound

Product 1

HCID 54284623HCID 54284623, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Cyclopropylcarbonyl chloride (1.7 mL, 18 mmol) was added dropwise during 15 minutes to an ice cold mixture containing (S)-3-(2,6-dimethylphenoxymethyl)piperidine hydrochloride (4.4 g, 17 mmol), aqueous sodium bicarbonate (75 mL), and ethyl acetate (100 mL). After the addition was complete, the reaction was stirred at room temperature for 1 hour, and the resulting ethyl acetate layer was separated and concentrated. The residue was dissolved in dry tetrahydrofuran (125 mL) under a dry nitrogen atmosphere and a 1M solution of lithium aluminum hydride in tetrahydrofuran (18.9 mL) was added dropwise. When the addition was complete, the reaction mixture was heated to reflux for 2 hours, then cooled to room temperature. Solid sodium sulfate decahydrate (10 g) was slowly added with stirring and the mixture was filtered. The filtrate was concentrated and chromatographed on silica gel, eluting with acetone/hexanes (1:3) to give (S)-1-cyclopropylmethyl-3-(2,6-dimethylphenoxymethyl)-piperidine as an oil.

Workup

  1. additionAfter the addition
  2. customthe resulting ethyl acetate layer was separated
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in dry tetrahydrofuran (125 mL) under a dry nitrogen atmosphere
  5. additiona 1M solution of lithium aluminum hydride in tetrahydrofuran (18.9 mL) was added dropwise
  6. additionWhen the addition
  7. temperaturethe reaction mixture was heated
  8. temperatureto reflux for 2 hours
  9. temperaturecooled to room temperature
  10. additionSolid sodium sulfate decahydrate (10 g) was slowly added
  11. stirringwith stirring
  12. filtrationthe mixture was filtered
  13. concentrationThe filtrate was concentrated
  14. customchromatographed on silica gel
  15. washeluting with acetone/hexanes (1:3)

Sources & evidence

ORD record
ord-31fe732cbf97400789bdba5261e3629b
Source dataset
uspto-grants-2001_07
Patent number
US06262078B1

Reaction notes

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