Potassium Carbonate → N-(t-Butyloxy)-2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3(R)-(3-picolyloxy)butanamide

HRID 2209722Notes

Reaction equation

HRID 2209722 reaction equation
[C:1]([O:5][NH:6][C:7](=[O:24])[C@H:8]([NH:12][S:13]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)(=[O:15])=[O:14])[C@H:9]([OH:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2].Cl.[N:26]1[CH:31]=[CH:30][CH:29]=[C:28]([CH2:32]Cl)[CH:27]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[C:1]([O:5][NH:6][C:7](=[O:24])[C@H:8]([N:12]([S:13]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)(=[O:15])=[O:14])[CH2:32][C:28]1[CH:27]=[N:26][CH:31]=[CH:30][CH:29]=1)[C@H:9]([O:11][CH2:32][C:28]1[CH:27]=[N:26][CH:31]=[CH:30][CH:29]=1)[CH3:10])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 233943-(Chloromethyl)pyridine hydrochloride2×HCID 22856309N-(t-butyloxy)-2(R)-[[4-methoxybenzenesulfonyl]-amino]-3(R)-hydroxybutanamide

Product 1

HCID 86749033N-(t-Butyloxy)-2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3(R)-(3-picolyloxy)butanamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(t-butyloxy)-2(R)-[[4-methoxybenzenesulfonyl]amino]-3(R)-hydroxybutanamide (3.04 g, 8.44 mmol) in dimethylformamide (150 mL) is added 3-picolyl chloride hydrochloride (1.45 g, 8.87 mmol) followed by potassium carbonate (11.65 g, 84.4 mmol). The reaction mixture is stirred at room temperature overnight, then heated to 45° C. for 5 hours. An additional amount of 3-picolyl chloride hydrochloride (692.0 mg, 4.23 mmol) is added at this point. The reaction mixture is stirred at 45° C. for 10 hours. The reaction mixture is diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo. The crude product is purified by silica gel chromatography (ethyl acetate, then 5% methanol/methylene chloride) to give N-(t-butyloxy)-2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3(R)-(3-picolyloxy)butanamide.

Workup

  1. temperatureheated to 45° C. for 5 hours
  2. stirringThe reaction mixture is stirred at 45° C. for 10 hours
  3. extractionextracted with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude product is purified by silica gel chromatography (ethyl acetate

Sources & evidence

ORD record
ord-74c43f554adf4ac2872e3f13ca8eea9e
Source dataset
uspto-grants-1995_10
Patent number
US05455258

Reaction notes

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