Triphenylphosphine → (R)-tert-butyl 2-((5-chloropyridin-3-yloxy)methyl)pyrrolidine-1-carboxylate

HRID 869629Notes

Reaction equation

HRID 869629 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[N:6][CH:7]=1.O[CH2:10][C@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].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>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([O:8][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH:5]=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 5823053-Hydroxy-5-chloropyridineHCID 688279N-(tert-Butoxycarbonyl)-D-prolinol

Product 1

HCID 21309710(R)-tert-butyl 2-((5-chloropyridin-3-yloxy)methyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 5-chloropyridin-3-ol (1.46 g, 11.28 mmol), (R)-tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate (2.27 g, 11.28 mmol), and triphenylphosphine (2.96 g, 11.28 mmol) in THF (50 mL) was added di-tert-butyl azodicarboxylate (DTAD) (2.60 g, 11.28 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h and warmed to room temperature. After being stirred at room temperature for 2 days, the mixture was concentrated in vacuo to afford a dark brown viscous oil. The residual oil was crystallized from isopropyl ether (IPE)-hexane, and formed precipitate was removed by filtration. The filtrate was concentrated in vacuo to afford a dark brown oil. The residual oil was purified by silica gel column chromatography (ethyl acetate/hexane 1:9 to 1:5) to afford crude 5.15 g (quant.) of the title compound as a colorless gel. The crude title compound was used for the next step without further purification.

Workup

  1. temperaturewarmed to room temperature
  2. stirringAfter being stirred at room temperature for 2 days
  3. concentrationthe mixture was concentrated in vacuo
  4. customto afford a dark brown viscous oil
  5. customThe residual oil was crystallized from isopropyl ether (IPE)-hexane
  6. customformed precipitate
  7. customwas removed by filtration
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto afford a dark brown oil
  10. customThe residual oil was purified by silica gel column chromatography (ethyl acetate/hexane 1:9 to 1:5)

Sources & evidence

ORD record
ord-6bcefa2b439544208585ed1e823d916c
Source dataset
uspto-grants-2015_03
Patent number
US08969383B2

Reaction notes

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