1,4-Dioxaspiro[4.5]decan-8-one → 8-[6-(1-Azetidinyl)-3-pyridinyl]-1,4-dioxaspiro[4.5]decan-8-ol

HRID 1015997Notes

Reaction equation

[N:1]1([C:5]2[CH:10]=[CH:9][C:8](Br)=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1.[Li]CCCC.[CH2:17]1[O:27][C:20]2([CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]2)[O:19][CH2:18]1>C1COCC1>[N:1]1([C:5]2[N:6]=[CH:7][C:8]([C:23]3([OH:26])[CH2:24][CH2:25][C:20]4([O:27][CH2:17][CH2:18][O:19]4)[CH2:21][CH2:22]3)=[CH:9][CH:10]=2)[CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: -78 °C

Procedure

2-azetidin-1-yl-5-bromopyridine (64 mg, 0.30 mmol) was dissolved in dry THF (1.5 mL) and cooled to −78° C., followed by the addition of n-BuLi (0.196 mL, 1.6 M in hexanes). Thirty minutes later, a solution of 1,4-cyclohexanedione mono-ethylene ketal (44.6 mg, 0.286 mmol) in dry THF (0.2 mL) was added dropwise at −78° C. with constant stirring. One hour later, the reaction was quenched with NH4Cl (aq) and slowly warmed to rt. The aqueous layer was extracted with CH2Cl2×3, dried, filtered and concentrated to give a crude, which was purified by flash column chromatography (100% EtOAc) to provide 35 mg (43%) of white solid product. MS (M+H+)=291.1.

Workup

customOne hour later, the reaction was quenched with NH4Cl (aq)
temperatureslowly warmed to rt
extractionThe aqueous layer was extracted with CH2Cl2×3
customdried
filtrationfiltered
concentrationconcentrated
customto give a crude, which
customwas purified by flash column chromatography (100% EtOAc)

Sources & evidence

ORD record: ord-b7090672bd724e39a3dc719d4f14a7ad
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07985730B2

Reaction notes

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