tert-Butyl 4-oxopiperidine-1-carboxylate → 4-Hydroxy-4-(6-methoxy-[1,5]naphthyridin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1511781Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][N:5]=[C:6]2[C:11]=1[N:10]=[C:9]([O:12][CH3:13])[CH:8]=[CH:7]2.[Li]CCCC.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>C1COCC1>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][C:29]([OH:32])([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=3)[N:5]=[CH:4][CH:3]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 8-bromo-2-methoxy-[1,5]naphthyridine (1 g, 4.18 mmol, prepared as in WO 2006/032466) in dry THF (20 mL) at −78° C. was added dropwise n-BuLi (2.5 M in hex, 5 mL, 1.2 eq). The mixture was stirred at −78° C. for 1 h before the dropwise addition of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (0.833 g, 4.2 mmol) in THF (5 mL). The mixture was stirred at −78° C. for another h and then slowly warmed to rt. The mixture was quenched by the addition of sat. aq. NH4Cl solution (10 mL) and extracted with EA. The combined org. layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by CC (hex/EA 1:1 to EA) to give the desired intermediate (1.0 g, 66.5%) as yellow oil.

Workup

temperatureslowly warmed to rt
customThe mixture was quenched by the addition of sat. aq. NH4Cl solution (10 mL)
extractionextracted with EA
dry with materiallayers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by CC (hex/EA 1:1 to EA)

Sources & evidence

ORD record: ord-5a4f6039cd414139a57c6a59e5ebfad8
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217029B2

Reaction notes

Loading…