Hydrochloric Acid → Benzyl 4-[3-cyclopropyl-1-(ethoxycarbonyl)but-3-en-1-yl]piperidine-1-carboxylate

HRID 1664790Notes

Reaction equation

HRID 1664790 reaction equation
Br[C:2](=[CH2:26])[CH2:3][CH:4]([CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:12][CH2:11]1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH:27]1([Mg]Br)[CH2:29][CH2:28]1.Cl>CCOCC.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH:27]1([C:2](=[CH2:26])[CH2:3][CH:4]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[CH2:12][CH2:11]2)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:29][CH2:28]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 86620119Benzyl 4-[3-bromo-1-(ethoxycarbonyl)but-3-en-1-yl]piperidine-1-carboxylateHCID 178418630HCID 178418630, compound2×

Product 1

HCID 67440127Benzyl 4-[3-cyclopropyl-1-(ethoxycarbonyl)but-3-en-1-yl]piperidine-1-carboxylateYield 24%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975Catalyst2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

Dichloro [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (137 mg, 0.187 mmol) was added to a solution of benzyl 4-[3-bromo-1-(ethoxycarbonyl)but-3-en-1-yl]piperidine-1-carboxylate (795 mg, 1.87 mmol) in ether (6 mL). The reaction mixture was cooled to 0° C. and cyclopropylmagnesium bromide (0.544 g, 3.75 mmol) was added. After 1 h, the mixture was warmed to ambient temperature. After 1 h, the mixture was cooled back to 0° C. and two additional portions of dichloro [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (137 mg, 0.187 mmol) and cyclopropylmagnesium bromide (544 mg, 3.75 mmol) were added. The mixture was warmed to ambient temperature. After 18 h, hydrochloric acid (10% in water) was added and the mixture was extracted with ether (2×). The combined organic extracts were washed with saturated aqueous sodium bicarbonate, water, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→50% hexanes/ethyl acetate) gave the title compound (173 mg). MS 386.2 (M+1).

Workup

  1. temperaturethe mixture was warmed to ambient temperature
  2. waitAfter 1 h
  3. temperaturethe mixture was cooled back to 0° C.
  4. temperatureThe mixture was warmed to ambient temperature
  5. waitAfter 18 h
  6. extractionthe mixture was extracted with ether (2×)
  7. washThe combined organic extracts were washed with saturated aqueous sodium bicarbonate, water
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by silica gel chromatography (100% hexanes→50% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-ca9e564f5aaa480997bfb1127fcc42c5
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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