Reaction #8867

Reaction equation

ammonium chloride

phenylacetaldehyde

tert-butyl 4-acetyl-4-(2-(tert-butyldimethylsilyloxy)eth-1-yl)piperidine-1-carboxylate

HMPA

LHMDS

→

tert-Butyl 4-(4-phenyl-3-hydroxy-1-oxobut-1-yl)-4-(2-(tert-butyldimethylsilyloxy)eth-1-yl)piperidine-1-carboxylate

Solvents

ether

THF

THF

THF

Conditions

Workup

1. 1
   Extractionextracted three times with ether
2. 2
   WashThe combined organic layers were washed with brine
3. 3
   Dryingdried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated
6. 6
   OtherThe residue was purified by flash chromatography (10 to 30% ethyl acetate in hexanes)
7. 7
   Otherto afford
8. 8
   Otherrecovered

Procedure

To a solution of tert-butyl 4-acetyl-4-(2-(tert-butyldimethylsilyloxy)eth-1-yl)piperidine-1-carboxylate (4.6 g, 12 mmol) in THF (120 mL) at −70° C. was added HMPA (20.7 mL, 120 mmol) and 1M LHMDS in THF (12 mL, 12 mmol). After 1 h, phenylacetaldehyde (5.7 g, 48 mmol) was added in THF (80 mL) over 10 min and the reaction was stirred for 1 h. The mixture was then poured into ether and aq. ammonium chloride solution and extracted three times with ether. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (10 to 30% ethyl acetate in hexanes) to afford recovered starting material (2.15 g) and the title product (2.2 g).

Source