Hydrochloric Acid → tert-Butyl 2-(hydroxymethyl)-1-oxo-8-azaspiro[4.5]decane-8-carboxylate

HRID 8753

Reaction equation

[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3]1.[CH:19](OCC)=[O:20].CC(C)([O-])C.[K+].Cl>C(OCC)C>[OH:20][CH2:19][CH:3]1[CH2:4][CH2:5][C:6]2([CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][CH2:11]2)[C:2]1=[O:1]

Participants

Conditions

Temperature: -78 °C

Procedure

tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate from Procedure 1, Step G (0.526 g, 2.08 mmol) was dried by evaporating with toluene (10 mL) three times in vacuo, dissolved in methyl-tert-butyl ether (5 mL), and cooled to −78° C. To this solution was added ethyl formate (0.336 mL, 4.15 mmol) and then potassium t-butoxide (0.466 g, 4.16 mmol). After 2 days, the reaction mixture was diluted with diethyl ether, poured into 2N HCl, and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 0.575 g. The residue was purified by flash chromatography eluting with 45% ethyl acetate/hexanes to give the title compound (0.303 g). MS/EI (acetonitrile/water): m/z 304 (M+1+Na) retention time=2.9 min.

Workup

customby evaporating with toluene (10 mL) three times in vacuo
dissolutiondissolved in methyl-tert-butyl ether (5 mL)
extractionextracted three times with diethyl ether
washwashed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customto afford 0.575 g
customThe residue was purified by flash chromatography
washeluting with 45% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-01aabc2e796f428ba758c5068521a6d6
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07091211B2

Linked notes

Loading…