1,4-Dioxaspiro[4.5]decan-8-one → HCID 67499969, compound

HRID 2197580Notes

Reaction equation

HRID 2197580 reaction equation
C([Li])CCC.Br[C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][N:8]=1.[O:14]1[C:18]2([CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)[O:17][CH2:16][CH2:15]1>C(OCC)C>[Cl:13][C:12]1[C:7]([C:21]2([OH:24])[CH2:22][CH2:23][C:18]3([O:17][CH2:16][CH2:15][O:14]3)[CH2:19][CH2:20]2)=[N:8][CH:9]=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 70163262-Bromo-3-chloropyridineHCID 178418339Butyllithium

Product 1

HCID 67499969HCID 67499969, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

To a −60° C. solution of n-butyl lithium (23 mL, 2.5M in hexane, 58.2 mmol) in diethyl ether (40 mL) was added a solution of 2-bromo-3-chloropyridine (Alfa, 8.0 g, 41.6 mmol) in diethyl ether (60 mL) over 15 minutes. The reaction mixture was stirred for 40 minutes followed by a slow addition (about 15 minutes) of a solution of 1,4-dioxaspiro[4.5]decan-8-one (Aldrich, 8.44 g, 54.0 mmol) in diethyl ether (100 mL), and stirred until reaction mixture warmed up to ambient temperature (about 3 hours). The mixture was quenched with saturated NH4Cl, diluted with ethyl acetate and washed with water. The organic layer was separated, concentrated and the residue crystallized from ethyl acetate-hexanes to obtain 5.5 g of the title compound. Two more crystallizations of the mother liquors yielded 1.61 g more material. Total yield 7.13 g (64%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.59 (d, J=12.69 Hz, 2H), 1.80 (d, J=12.69 Hz, 2H), 1.94 (td, J=12.69, 4.36 Hz, 2H), 2.30-2.41 (m, 2H), 3.88 (s, 4H), 5.36 (s, 1H), 7.36 (dd, J=7.93, 4.76 Hz, 1H), 7.88 (dd, J=7.93, 1.59 Hz, 1H), 8.48 (dd, J=4.76, 1.59 Hz, 1H). MS (DCI) m/z 270.10 (M+H)+.

Workup

  1. stirringstirred until reaction mixture
  2. customThe mixture was quenched with saturated NH4Cl
  3. additiondiluted with ethyl acetate
  4. washwashed with water
  5. customThe organic layer was separated
  6. concentrationconcentrated
  7. customthe residue crystallized from ethyl acetate-hexanes

Sources & evidence

ORD record
ord-8b81a2eceb4445e99cb202c7ed225dc9
Source dataset
uspto-grants-2012_12
Patent number
US08338603B2

Reaction notes

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