Reaction #8846

Reaction equation

ammonium chloride

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

lithium diisopropylamide mono(tetrahydrofuran)

propionaldehyde

→

clear oil

Yield 120.9%

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

Yield 120.9%

Solvents

diethyl ether

Conditions

Workup

1. 1
   Otherby evaporating with toluene (10 mL) three times in vacuo
2. 2
   workup.DISSOLUTIONdissolved in tetrahydrofuran (100 mL)
3. 3
   workup.WAITAfter 5 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 Step G (4.5 g, 17.8 mmol) was dried by evaporating with toluene (10 mL) three times in vacuo, dissolved in tetrahydrofuran (100 mL), and cooled to −78° C. To this solution was added lithium diisopropylamide mono(tetrahydrofuran) (24 mL, 36 mmol, 1.5 M in cyclohexane). The reaction mixture was stirred for 30 min at −78° C. before adding propionaldehyde (2.6 mL, 36 mmol). After 5 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 20–30% ethyl acetate in hexanes to give the title compound (4.75 g).

Source