Triphenylphosphine → tert-butyl 4-({(2S)-2-[(2,5-dichloropyridin-3-yl)oxy]propanoyl}amino)piperidine-1-carboxylate

HRID 1026543Notes

Reaction equation

HRID 1026543 reaction equation
[OH:1][C@H:2]([CH3:19])[C:3]([NH:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)=[O:4].[Cl:20][C:21]1[C:26](O)=[CH:25][C:24]([Cl:28])=[CH:23][N:22]=1.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>O.O1CCCC1>[Cl:20][C:21]1[C:26]([O:1][C@@H:2]([CH3:19])[C:3]([NH:5][CH:6]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)=[O:4])=[CH:25][C:24]([Cl:28])=[CH:23][N:22]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 98989172,5-Dichloropyridin-3-OlHCID 68500407tert-butyl 4-{[(2R)-2-hydroxypropanoyl]amino}piperidine-1-carboxylate

Product 1

HCID 86671388tert-butyl 4-({(2S)-2-[(2,5-dichloropyridin-3-yl)oxy]propanoyl}amino)piperidine-1-carboxylateYield 81.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a tetrahydrofuran solution (148 ml) of tert-butyl 4-{[(2R)-2-hydroxypropanoyl]amino}piperidine-1-carboxylate (5.13 g), 2,5-dichloropyridin-3-ol (3.40 g) and triphenylphosphine (6.41 g) was added dropwise at room temperature a tetrahydrofuran solution (40 ml) of di-tert-butyl azodicarboxylate (5.63 g) over 10 minutes. The reaction solution was stirred at room temperature for 1 hour, then poured into water, and extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford tert-butyl 4-({(2S)-2-[(2,5-dichloropyridin-3-yl)oxy]propanoyl}amino)piperidine-1-carboxylate (6.40 g).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed sequentially with water and saturated sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8031a6ef764b43deae64f70a2479ef62
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

Loading…