Potassium Phosphate, Tribasic → tert-Butyl 2-(4-cyclopropyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

HRID 1848460Notes

Reaction equation

HRID 1848460 reaction equation
Br[C:2]1[C:6](=[O:7])[O:5][CH2:4][C:3]=1[N:8]1[CH2:12][CH2:11][C:10]2([CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[C:9]1=[O:25].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P([CH:47]2[CH2:52][CH2:51]CCC2)C2CCCCC2)CCCCC1.C1(B(O)O)CC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:51]1([C:2]2[C:6](=[O:7])[O:5][CH2:4][C:3]=2[N:8]2[CH2:12][CH2:11][C:10]3([CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[C:9]2=[O:25])[CH2:52][CH2:47]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 86709468tert-Butyl 2-(4-bromo-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

Product 1

HCID 86709469tert-Butyl 2-(4-cyclopropyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

In a microwave vial, tert-butyl 2-(4-bromo-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (90 mg, 0.22 mmol) was dissolved in toluene (2 mL) and water (0.2 mL). Potassium phosphate (138 mg, 0.650 mmol), tricyclohexylphosphine (18 mg, 0.065 mmol), cyclopropylboronic acid (74.5 mg, 0.867 mmol) and palladium acetate (4.87 mg, 0.022 mmol) were added. The reaction mixture was de-gassed and heated at 100° C. for 12 hours. After cooling to room temperature, the reaction mixture was concentrated and the resulting residue was dissolved in EtOAc (50 mL), washed with water (30 mL) and brine (30 mL), dried over sodium sulfate, and filtered. Removing the solvent gave crude product that was purified by column chromatography eluting with 0-100% EtOAc/hexane gradient to yield the title compound. 1H NMR (500 MHz, CDCl3) δ 5.20 (s, 2H), 4.22 (m, 2H), 3.99 (m, 2H), 3.05 (m, 2H), 2.09 (m, 2H), 1.92 (m, 2H), 1.60 (m, 2H), 1.56 (m, 10H), 1.02 (m, 2H), 0.82 (m, 2H).

Workup

  1. customThe reaction mixture was de-gassed
  2. temperatureAfter cooling to room temperature
  3. concentrationthe reaction mixture was concentrated
  4. dissolutionthe resulting residue was dissolved in EtOAc (50 mL)
  5. washwashed with water (30 mL) and brine (30 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customRemoving the solvent
  9. customgave crude product that
  10. customwas purified by column chromatography
  11. washeluting with 0-100% EtOAc/hexane gradient

Sources & evidence

ORD record
ord-1ed48d9f5b4043b08fc6dce16996da41
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

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