Triphenylphosphine → 1,1-Dimethylethyl 4-[(1R,2S)-2-[2-[4-(methylsulfonyl)phenoxy]ethyl]cyclopropyl]-1-piperidinecarboxylate

HRID 1850754Notes

Reaction equation

HRID 1850754 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)(=[O:4])=[O:3].O[CH2:13][CH2:14][C@@H:15]1[CH2:17][C@@H:16]1[CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1.C(OCC)(=O)C.O>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:13][CH2:14][C@@H:15]2[CH2:17][C@@H:16]2[CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:20][CH2:19]2)=[CH:7][CH:6]=1)(=[O:3])=[O:4]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 1233504-(Methylsulfonyl)phenolHCID 5363146Diisopropyl azodicarboxylateHCID 66935605HCID 66935605, compound

Product 1

HCID 708559581,1-Dimethylethyl 4-[(1R,2S)-2-[2-[4-(methylsulfonyl)phenoxy]ethyl]cyclopropyl]-1-piperidinecarboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

4-(methylsulfonyl)phenol (17 mg, 0.1 mmol), tert-butyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl)piperidine-1-carboxylate (27 mg, 0.1 mmol), and triphenylphosphine (70 mg, 0.21 mmol) were dissolved in tetrahydrofuran (1 mL) under an atmosphere of nitrogen and cooled at 0° C. DIAD (32 mg, 0.14 mmol) was added and the resulting mixture was warmed to RT and stirred overnight. The mixture was diluted with ethyl acetate (10 mL) and water (5 mL), and the layers were separated. The organic layer was washed with brine (2×10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by MS directed HPLC (30 minute, standard gradient 0-90% acetonitrile/water 0.1% formic acid buffer) and the fractions containing product combined. The solution was concentrated to dryness via GenoVac to afford the title compound. LC/MS (m/z): 424 (M+H)+. GPR119 Human EC50: 0.9 nM

Workup

  1. temperaturethe resulting mixture was warmed to RT
  2. customthe layers were separated
  3. washThe organic layer was washed with brine (2×10 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by MS
  8. customHPLC (30 minute, standard gradient 0-90% acetonitrile/water 0.1% formic acid buffer)
  9. additionthe fractions containing product
  10. concentrationThe solution was concentrated to dryness via GenoVac

Sources & evidence

ORD record
ord-b9f416e08a384206b232ba7a720e5c30
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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