Triphenylphosphine → 2-{(SR)-1-[(3SR,4SR)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethoxy}-5-chloro-pyridine

HRID 2191109Notes

Reaction equation

HRID 2191109 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[Cl:36][C:37]1[CH:38]=[CH:39][C:40]([OH:43])=[N:41][CH:42]=1.[CH2:44]([N:51]1[CH2:56][CH2:55][CH:54]([CH:57](O)[CH3:58])[CH:53]([C:60]2[CH:65]=[CH:64][C:63]([Cl:66])=[CH:62][CH:61]=2)[CH2:52]1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>C1COCC1>[CH2:44]([N:51]1[CH2:56][CH2:55][CH:54]([CH:57]([O:43][C:40]2[CH:39]=[CH:38][C:37]([Cl:36])=[CH:42][N:41]=2)[CH3:58])[CH:53]([C:60]2[CH:65]=[CH:64][C:63]([Cl:66])=[CH:62][CH:61]=2)[CH2:52]1)[C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 68475389(RS)-1-[(3SR,4SR)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanolHCID 1785160645-chloropyridin-2-ol

Product 1

HCID 684715562-{(SR)-1-[(3SR,4SR)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethoxy}-5-chloro-pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
2.5 °C

Procedure

In a 50 mL three-necked round bottom flask (flame dried) charged with a magnetic stirrer and under inert atmosphere to 1080 mg polymer bound triphenylphosphine (3 mmol/g) in 10 mL THF was added 502 mg (2.18 mmol) di-tert-butyl azodicarboxylate in 5 mL THF and 265 mg (2.04 mmol) 5-chloro-2-hydroxypyridine in 10 mL THF at 0-5° C. The brownish suspension was stirred for 20 min at 0-5° C. 450 mg (1.36 mmol) (RS)-1-[(3SR,4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanol in 5 mL THF was added and the ice bath was removed and the reaction was stirred for 63 h at room temperature. The suspension was filtered over a Dicalit-filter. The filtrate was concentrated under vacuum and the residue was purified by chromatography over silica eluting with a gradient formed from i-propanol and heptane to yield after evaporation of the product containing fractions 480 mg (80%) of the title compound as yellow viscous oil. MS (m/e): 441.2 [(M+H)+].

Workup

  1. temperatureIn a 50 mL three-necked round bottom flask (flame dried)
  2. customthe ice bath was removed
  3. stirringthe reaction was stirred for 63 h at room temperature
  4. filtrationThe suspension was filtered over a Dicalit-filter
  5. concentrationThe filtrate was concentrated under vacuum
  6. customthe residue was purified by chromatography over silica eluting with a gradient
  7. customformed from i-propanol and heptane
  8. customto yield
  9. customafter evaporation of the product
  10. additioncontaining fractions 480 mg (80%) of the title compound as yellow viscous oil

Sources & evidence

ORD record
ord-8417ff0362524b7ca5777e7ee62d4f48
Source dataset
uspto-grants-2012_12
Patent number
US08324248B2

Reaction notes

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