All Notebooks | Help | Support | About
20th August 2014 @ 23:39

Synthesis of an ether with a 4 atom chain to further explore the effect of chain length on the ether series. 

GitHub Issue: #254

Literature ref: 10.1021/jo901707x

Reaction Scheme

Procedure

Started 3:20pm

(R)-2-amino-3-phenylpropan-1-ol (100 mg, 0.66 mmol, 1.1 equiv) was added to 1.5 mL toluene along with JU 8 (157 mg, 0.59 mmol, 1 equiv), potassium hydroxide (110 mg, 1.96 mmol, 3.3 equiv) and 18-crown-6 (9 mg, 0.03 mmol, 0.05 equiv). The reaction was stirred at 40°C (bath temperature) for 1 h. Analysis by TLC showed the reaction was complete.

TLC JU 23-1 50:50 EtOAc:Hex 1 h.jpg

The reaction was stopped and cooled before diluting with water (6 mL). The aqueous layer was extracted with EtOAc (4 x 5 mL). The combined organic layers were washed with water (3 x 6 mL) until pH 9, then with brine (5 mL). The organic layers were dried over Na2SO4 and the solvent removed by rotary evaporation. The crude product (129 mg, 58%) was dried in vacuo and analysed by 1H NMR.

1H NMR, crude, DMSO, 200 MHz

JU 23-1 crude 200 MHz.pdf
JU 23-1 crude.zip

The crude material was purified using the biotage isolera, see run details below.

 

1H NMR, green frac, DMSO, 200 MHz

JU 23-1 green frac 200 MHz.pdf
JU 23-1 green frac pure.zip

1H NMR, yellow frac, DMSO, 200 MHz

JU 23-1 yellow frac 200 MHz.pdf
JU 23-1 yellow frac pure.zip


From the NMRs, it appears that this reaction was unsuccessful, neither SM or product can be seen. This needs to be attempted again, this time by protecting the free amine first before coupling to the triazolopyrazine. 

 

HIRAC

HIRAC JU 23-1.pdf

InChI strings

InChI=1S/C11H6Cl2N4/c12-8-3-1-7(2-4-8)11-16-15-10-6-14-5-9(13)17(10)11/h1-6H

and

InChI=1S/C9H13NO/c10-9(7-11)6-8-4-2-1-3-5-8/h1-5,9,11H,6-7,10H2/t9-/m1/s1

to

InChI=1S/C20H18ClN5O/c21-16-8-6-15(7-9-16)20-25-24-18-11-23-12-19(26(18)20)27-13-17(22)10-14-4-2-1-3-5-14/h1-9,11-12,17H,10,13,22H2/t17-/m1/s1

SMILES

ClC1=CN=CC2=NN=C(C3=CC=C(Cl)C=C3)N21

and

OC[C@H](N)CC1=CC=CC=C1

to

ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OC[C@H](N)CC4=CC=CC=C4)N32

Linked Posts
This post is linked by:
Attached Files
Reaction Scheme JU 23-1.png
HIRAC JU 23-1.pdf
TLC JU 23-1 50:50 EtOAc:Hex 1 h.jpg
JU 23-1 crude 200 MHz.pdf
JU 23-1 crude.zip
JU 23-1 yellow frac pure.zip
JU 23-1 green frac pure.zip
JU 23-1 green frac 200 MHz.pdf
JU 23-1 yellow frac 200 MHz.pdf