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17th July 2017 @ 19:03

Scheme: 

DaraprimS3Scheme.png

SM/P

3-(4-chlorophenyl)-4-methoxyhexanenitrile

Guanidine chloride

Sodium methoxide

product

mw

221.68

95.53

54.02

248.71

Equiv

1.00

3.00

3.00

1.00

mmol

0.50

1.45

1.49

0.50

g

0.11

0.143

0.080

0.124

mL

 

 

 

 

g/mL

 

 

1.059

 

Procedure: 

7/7/17 Guanidine hydrochloride (0.143 g, 1.45 mmol, 3 eq) and sodium methoxide (0.080 g, 1.49 mmol, 3 eq) were dissolved in ethanol (1.13 mL) and stirred for 5 minutes. A solution of 3-(4-chlorophenyl)-4-methoxyhexanenitrile (o.11 g, 0.50 mmol, 1 eq) in ethanol (0.37 mL) was added. The reaction mixture was heated under reflux for 18 h.

7/8/17 Reaction removed from reflux at 2:30 pm.

TLC in 30:70 EtOAc in Hexanes. Spots are UV active.

SM (left)= 3-(4-chlorophenyl)-4-methoxyhexanenitrile

Cospot (Middle)

Product (Right) 

DaraprimS3_TLC.jpg

7/10/17 The reaction mixture was diluted with dichloromethane. Saturated NaCl was added and the mixture was extracted three times with dichloromethane. Organic extracts were combined and dried over MgSO4. Solvent was removed under reduced pressure. NMR obtained. 

JSLT_Daraprim_NMRcrude_CDCl3.png

7/11/17 Product was crystallized from methanol. Too much methanol was added the first time and no crystals formed.

7/12/17 Solvent was removed under reduced pressure. Product was crystallized from methanol and placed in the freezer overnight.

7/13/17 Solvent was removed carefully with a pipette, and crystals were washed with cold methanol. NMR obtained. 

JSLT_DaraprimS3_NMR_CDCl3.jpg

7/20/17 Crystals were derivitized in order to run GC-MS. A small sample of the crystals (1 mg) was placed in a microcentrifuge tube and a 40 mg/mL solution of methoxyamine hydrochloride in pyridine (10 μL) was added. The tube was heated to 30°C for 90 minutes in a standard heatblock. After 90 minutes, N-methyl-N-trimethylsilyltrifluoroacetamide (90 μL) was added and the samples were heated at 37°C for 30 minutes. (Fiehn, O.; Kind, T. Metabolomics 2009, 3–18.

This added TMS groups as shown:

 

Derivatization.png

 The GC-MS showed an mpeak at 392 and an [m-15]peak at 377


pyrimethamineGCMS2.png
pyrimethamineGCMS.png
Attached Files
DaraprimS3_TLC.jpg
JSLT_DaraprimS3_NMR_CDCl3.jpg
JSLT_Daraprim_NMRcrude_CDCl3.png
DaraprimS3Scheme.png
Derivatization.png
pyrimethamineGCMS.png
pyrimethamineGCMS2.png