2,2,6,6-Tetramethylpiperidine → HCID 67280685, compound

HRID 1694570Notes

Reaction equation

HRID 1694570 reaction equation
C([Li])CCC.CC1(C)CCCC(C)(C)N1.[Cl:16][C:17]1[C:25]([F:26])=[N:24][CH:23]=[CH:22][C:18]=1[C:19]([OH:21])=[O:20].[O:27]1[C:31]2([CH2:36][CH2:35][C:34](=O)[CH2:33][CH2:32]2)[O:30][CH2:29][CH2:28]1>CCCCCC.O.O1CCCC1>[Cl:16][C:17]1[C:18]2[C:19](=[O:21])[O:20][C:34]3([CH2:35][CH2:36][C:31]4([O:30][CH2:29][CH2:28][O:27]4)[CH2:32][CH2:33]3)[C:22]=2[CH:23]=[N:24][C:25]=1[F:26]

Participants

8

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 121754283-Chloro-2-fluoropyridine-4-carboxylic acidHCID 178418339Butyllithium

Product 1

HCID 67280685HCID 67280685, compoundYield 49.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

At −60° C., n-butyllithium (1.50 M hexane solution) (75.9 mL) was dropwise added to tetrahydrofuran (100 mL) solution of 2,2,6,6-tetramethylpiperidine (12.5 g), and stirred at −78° C. for 30 minutes. At −78° C., 3-chloro-2-fluoroisonicotinic acid (5.00 g) was added to the reaction liquid, and stirred at −78° C. for 2 hours. Then, at −78° C., tetrahydrofuran (50 mL) solution of 1,4-dioxaspiro[4.5]decan-8-one (5.78 g) was added to the reaction liquid, and stirred for 30 minutes at −78° C. The reaction liquid was warmed up under cooling with ice, and water and hexane were added thereto in that order. The aqueous layer and the organic layer were separated from each other, then the aqueous layer was made acidic (pH of 1 to 2) with 2 M hydrochloric acid added thereto and the stirred at room temperature for 2 hours. The formed solid was taken out through filtration, washed with water, and dried under reduced pressure to obtain the entitled compound (4.39 g, 49%) as a pale brown solid.

Workup

  1. stirringstirred at −78° C. for 2 hours
  2. stirringstirred for 30 minutes at −78° C
  3. customThe reaction liquid
  4. temperaturewas warmed up
  5. additionwere added
  6. customThe aqueous layer and the organic layer were separated from each other, then the aqueous layer
  7. additionadded
  8. stirringthe stirred at room temperature for 2 hours
  9. filtrationThe formed solid was taken out through filtration
  10. washwashed with water
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-3a148249187a437c925d028af8785908
Source dataset
uspto-grants-2012_04
Patent number
US08158791B2

Reaction notes

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