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17th July 2017 @ 18:10

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Compound 

MW(m) 

Mol(Mmol 

Mol(M) 

Mass 

Density 

Volume(mL) 

Equiv  

LDA, 2.0 M in 20 ML dry THF 

 

 

20.78 

2 

 

 

10.4 

1.05 

4-chlorobenzeneacetonitrile 

 

151.59 

19.79 

 

3000 mg 

1.059 

1.73 

1 

propionyl chloride 

92.52 

 

 

 

 

 

1 

Product  

 

207.66 

19.79 

 

4110 mg 

 

 

1 

 

 

 5/22/17 – A dry 1-neck 250 mL 24/40 round bottom flask with septum was used. Once under Argon the 20 mL dry THF and 10.4 mL 2.0 M LDA gave a light-med brown-orange solution, which was cooled to ~ -80 ˚C with dry ice/acetone.  A clear, colorless solution of 4-chlorobenzeneacetonitrile in 30 mL dry THF was then added to the aforementioned solution at about 4 drops/sec down the cooled side of the 250 mL RB flask to give a clear light-med brown-orange solution, which was stirred for approximately 10 minutes at ~ -80 ˚C.  With dry ice/acetone bath still in place, a clear, colorless solution of propionyl chloride in 5 mL dry THF was added dropwise at about ~ 2 drops/second to give a cloudy light-medium tan suspension, which was allowed to stir overnight and warm to room temperature slowly as the cooling bath warmed. 

5/23/17 -  In the morning a concentrated darkish yellow suspension was present.  The reaction was quenched at RT with saturated aqueous ammonium chloride which afforded a clear, light-medium red-orange solution with a white/colorless solid in the bottom. 

The reaction mixture was transferred to a separatory funnel, and the organic layer was washed with H2O (the NH4Cl solid dissolved with addition of H2O), brine, dried over MgSO4, and concentrated to a brown liquid.   

To the resulting crude product was added a minimal amount of CH2Cl2, followed by a minimal amount of dry silica.  The volatiles were removed and the dry silica was stored in the fridge overnight.  

5/24/17 - The resulting silica was dry transferred onto a silica column. 

The column was eluted with 10:90 EtOAc/Hexanes until the last product began to come off column, followed by EtOAc to completely remove it. 

Fractions 26-50 and small Erlenmeyer’s A-E were collected and concentrated on high vacuum, and NMR was obtained -- labeled spot “3” -- (1.4g, 6.74 mmol, 34% yield)  

JSLT_DaraprimS1_TLC.pdf

 

JSLT_daraprim_step1_spot3_PROTON_cdcl3_01.pdf
 

JSLT_DaraprimS1_GCMS.pdf
JSLT_Daraprim_S1_GCMS2.pdf
JSLT_DaraprimS1_GCMS3.pdf
Attached Files
JSLT_daraprim_step1_spot3_PROTON_cdcl3_01.pdf
JSLT_DaraprimS1_TLC.pdf
JSLT_DaraprimS1_GCMS.pdf
JSLT_DaraprimS1_GCMS3.pdf
JSLT_Daraprim_S1_GCMS2.pdf
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