Hydrochloric Acid → 4-(3-Oxopyrrolidin-1-yl)-pyridine-2-carboxylic acid phenylamide

HRID 1052013Notes

Reaction equation

HRID 1052013 reaction equation
[C:1]1([NH:7][C:8]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:20][CH2:19][CH:18]([OH:21])[CH2:17]3)[CH:13]=[CH:12][N:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.Cl.C(Cl)(Cl)Cl>ClCCl.CS(C)=O>[C:1]1([NH:7][C:8]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:20][CH2:19][C:18](=[O:21])[CH2:17]3)[CH:13]=[CH:12][N:11]=2)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6212ChloroformHCID 81531DiisopropylethylamineHCID 866958274-(3-Hydroxypyrrolidin-1-yl)-pyridine-2-carboxylic acid phenylamide

Product 1

HCID 866958284-(3-Oxopyrrolidin-1-yl)-pyridine-2-carboxylic acid phenylamideYield 50%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(3-Hydroxypyrrolidin-1-yl)-pyridine-2-carboxylic acid phenylamide (259 mg, 0.92 mmol) in dichloromethane (5 mL) and dimethylsulfoxide (2.5 mL) was cooled in an ice bath. Diisopropylethylamine (0.48 mL, 2.8 mmol) was added and stirred for 5 minutes. A solution of sulfur trioxide-pyridine complex (0.44 g, 2.8 mmol) in DMSO (2.5 mL) was added dropwise. The reaction was stirred at 0° C. for 3 hours. To the reaction was added 1 M hydrochloric acid (6 mL) and chloroform. The layers were separated. The aqueous layer was treated with saturated aqueous sodium bicarbonate until pH=6. Extraction twice with chloroform gave a crude residue. Purification by chromatography on silica gel (12 g) eluted with chloroform:methanol 39:1 gave the title compound (133 mg, 0.46 mmol, 50%).

Workup

  1. stirringThe reaction was stirred at 0° C. for 3 hours
  2. customThe layers were separated
  3. additionThe aqueous layer was treated with saturated aqueous sodium bicarbonate until pH=6
  4. extractionExtraction twice with chloroform
  5. customgave a crude residue
  6. customPurification by chromatography on silica gel (12 g)
  7. washeluted with chloroform:methanol 39:1

Sources & evidence

ORD record
ord-3cb8cd27f2884d35b7a873fa070caa7b
Source dataset
uspto-grants-2016_07
Patent number
US09388176B2

Reaction notes

Loading…