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24th February 2016 @ 03:24

Reduction of ester with new batch of LiAlH4 in THF following failed reduction of carboxylic acid in Synthesis of 2-phenylpropane-1,3-diol (AEW 268-1)

 

 

AEW 266-2 (2.34 g, 12.1 mmol, 1.00 equiv.) was dissolved in anhydrous diethyl ether (120 mL) and cooled to 0 ˚C. LiAlH4 (1 M in THF, 7.71 mL, 7.71 mmol, 0.64 equiv.) was added dropwise and the reaction mixture stirred for ten mins at 0 ˚C and then ten mins after reaching rt. Reaction mixture refluxed for 20 h. 

Cooled to RT and then in an ice bath. Acetone added dropwise to quench excess LAH and then a saturated soln of Rochelle's salt was added (dropwise at start then with pouring, 80 mL). Stirred at 0 ˚C and then rt overnight. Work up: EtOAc/Sodium hydrogen carbonate soln.

 

Data:

AEW 269-1.dx
AEW 269-2.dx
AEW 269-2.zip

AEW 269-2 crude.png

AEW 269-1.png
AEW 269-1.dx
Attached Files
24th February 2016 @ 02:21


 

AEW 205-1 (200 mg, 0.67 mmol, 1 equiv) was suspended in anhydrous toluene (4 mL) along with potassium hydroxide (132 mg, 2.36 mmol, 3.5 equiv) and 18-crown-6 (12 mg, 0.05 mmol, 0.07 equiv). AEW 221-1 (150 mg, 0.67 mmol, 1 equiv) was dissolved in anhydrous toluene and added to the reaction mixture whilst stirring at rt for ten mins. Reaction heated to 40 ˚C with stirring.

The sample was cooled to room temperature and diluted with 4 mL of water. The mixture was extracted with EtOAc (3 x 10 mL). The combined organic layer was washed with water (1 x 4 mL) until the aqueous layer became neutral followed by brine (3 mL) and dried over Na2SO4. The orange/yellow fluoro solution was filtered and dried under reduced pressure and in vacuo to yield an orange oil that was dried at the high vac.

Crude NMR looks promising but a mixture of product: SM 1:0.2. Will deprotect crude material.

 

Data:


InChi:

InChI=1S/C11H9ClF2N4O/c1-7(3-2-4-19-11(13)14)10-17-16-9-6-15-5-8(12)18(9)10/h2-3,5-6,11H,1,4H2/b3-2-

and

InChI=1S/C13H18O3/c14-10-12(11-6-2-1-3-7-11)16-13-8-4-5-9-15-13/h1-3,6-7,12-14H,4-5,8-10H2

to

InChI=1S/C25H24F2N4O4/c26-25(27)34-19-11-9-18(10-12-19)24-30-29-21-14-28-15-22(31(21)24)33-16-20(17-6-2-1-3-7-17)35-23-8-4-5-13-32-23/h1-3,6-7,9-12,14-15,20,23,25H,4-5,8,13,16H2


ClC1=CN=CC2=NN=C(C3=CC=C(OC(F)F)C=C3)N21

and

OCC(OC1OCCCC1)C2=CC=CC=C2

to

FC(F)OC(C=C1)=CC=C1C2=NN=C3N2C(OCC(OC4OCCCC4)C5=CC=CC=C5)=CN=C3