1,4-Dioxaspiro[4.5]decan-8-one → 6-(8-Hydroxy-1,4-dioxaspiro[4.5]dec-8-yl)nicotinonitrile
Reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.C([Li])CCC.[CH2:15]1[O:25][C:18]2([CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)[O:17][CH2:16]1>C1COCC1.CCCCCC>[OH:24][C:21]1([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=2)[CH2:22][CH2:23][C:18]2([O:17][CH2:16][CH2:15][O:25]2)[CH2:19][CH2:20]1Participants
Conditions
- Temperature
- 20 °C
Procedure
A solution of 6-bromonicotinonitrile (2 g, 0.011 mol) in 50 mL of dry THF and 15 mL of dry hexane under argon was cooled to −100° C. in a liquid nitrogen-Et2O bath. n-Butyllithium (7.5 mL, 0.011 mol, 1.6 M solution in hexane) was added rapidly dropwise so that the internal temperature did not exceed −95° C. The orange solution was stirred for an additional 10 min at −100° C. to −95° C. and then treated dropwise over 10 min with a solution of 1,4-cyclohexanedione monoethylene ketal (1.8 g, 0.011 mol) in 55 mL of dry THF, again carefully maintaining the temperature below −95° C. The reaction mixture was stirred for 10 min at −100° C. to −95° C., allowed to warm to 20° C. and poured into ice water (400 mL). The organic layer was separated, and the aqueous layer was extracted twice with Et2O (200 mL). The combined organic extracts were dried over MgSO4 and evaporated to give 2.8 g of white crystalline solid. Trituration with Et2O afforted 1.9 g (67% yield) of white crystals: MS: 261 (M+1)+.
Workup
- customdid not exceed −95° C
- temperatureagain carefully maintaining the temperature below −95° C
- stirringThe reaction mixture was stirred for 10 min at −100° C. to −95° C.
- customThe organic layer was separated
- extractionthe aqueous layer was extracted twice with Et2O (200 mL)
- dry with materialThe combined organic extracts were dried over MgSO4
- customevaporated
Sources & evidence
- ORD record
- ord-26d3479d8d3d4c58b3b99b5c8dc0e726
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08729063B2
Reaction notes
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