Reaction #8848

Reaction equation

ammonium chloride

tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate

lithium diisopropylamide mono(tetrahydrofuran)

acetaldehyde

→

clear oil

tert-Butyl 2-(1-hydroxyeth-1-yl)-1-oxo-8-azaspiro[4.5]decane 8-carboxylate

Solvents

diethyl ether

Conditions

Workup

1. 1
   Otherby evaporating with toluene (5 mL) three times in vacuo
2. 2
   workup.DISSOLUTIONdissolved in tetrahydrofuran (50 mL)
3. 3
   workup.WAITAfter 10 min
4. 4
   Extractionextracted three times with diethyl ether
5. 5
   Washwashed with brine
6. 6
   Dryingdried over sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated

Procedure

tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate from Procedure 1, Step G (1.2 g, 4.70 mmol) was dried by evaporating with toluene (5 mL) three times in vacuo, dissolved in tetrahydrofuran (50 mL), and cooled to −78° C. To this solution was added lithium diisopropylamide mono(tetrahydrofuran) (6.3 mL, 9.4 mmol, 1.5 M in cyclohexane). The reaction mixture was stirred for 35 min at −78° C. before adding acetaldehyde (0.527 mL, 9.4 mmol). After 10 min, the reaction mixture was diluted with diethyl ether, poured into saturated ammonium chloride, and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 6.7 g of a clear oil. The residue was purified by flash chromatography eluting with 20–40% ethyl acetate/hexanes to give the title compound (0.620 g).

Source