2-Bromopyridine → HCID 21187637, compound

HRID 1809837Notes

Reaction equation

HRID 1809837 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[CH2:13]1[O:23][C:16]2([CH2:21][CH2:20][C:19](=[O:22])[CH2:18][CH2:17]2)[O:15][CH2:14]1>CCOCC>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:19]1([OH:22])[CH2:20][CH2:21][C:16]2([O:23][CH2:13][CH2:14][O:15]2)[CH2:17][CH2:18]1

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 178418339Butyllithium

Product 1

HCID 21187637HCID 21187637, compoundYield 33.6%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-bromopyridine (14 g, 88.6 mmol) in anhydrous ether (300 mL) cooled at −78° C. was slowly added a solution of 2.5 M butyl lithium (36 mL). After the addition, stirring was continued at −78° C. for 1 hour. To it was slowly added a solution of 1,4-cyclohexanedione mono-ethylene ketal (15 g, 96 mmol) in anhydrous ether (300 mL). When the addition was complete, the mixture was allowed to warm to 0° C. and stirring was continued for 1 hour. The reaction was quenched by the addition of an aqueous solution (100 mL) of ammonium chloride (4.5 g). The organic phase was separated and the aqueous phase was extracted with methylene chloride 4 times. The combined organic phases were dried over MgSO4 and concentrated. Crystallization from EtOAc provided 7 g of the desired product. The mother liquid was purified on silica gel eluting with 10% MeOH/EtOAc to give 3 g of the desired product. MS calculated (M+H)+236. Found 236.0.

Workup

  1. additionAfter the addition
  2. additionWhen the addition
  3. stirringstirring
  4. waitwas continued for 1 hour
  5. customThe reaction was quenched by the addition of an aqueous solution (100 mL) of ammonium chloride (4.5 g)
  6. customThe organic phase was separated
  7. extractionthe aqueous phase was extracted with methylene chloride 4 times
  8. dry with materialThe combined organic phases were dried over MgSO4
  9. concentrationconcentrated
  10. customCrystallization from EtOAc

Sources & evidence

ORD record
ord-4b26cccc1b8c4f868b776d64f0a9a730
Source dataset
uspto-grants-2013_01
Patent number
US08362003B2

Reaction notes

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