5-Bromo-2-methylpyridine → HCID 67993162, compound

HRID 244276Notes

Reaction equation

HRID 244276 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:8])=[N:6][CH:7]=1.CON(C)[C:12]([CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=[O:13]>C1COCC1>[CH3:8][C:5]1[CH:4]=[CH:3][C:2]([C:12]([CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)=[O:13])=[CH:7][N:6]=1

Participants

4

Reactant 2

HCID 12010205-Bromo-2-methylpyridineHCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

Product 1

HCID 67993162HCID 67993162, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-bromo-2-methylpyridine (1.25 g, 7.2 mmol) in anhydrous THF (15 mL) at −40° C. under an argon atmosphere, lithium dibutyl(isopropyl)magnesate (5.2 mL, 0.7 M, 3.6 mmol) was added. The stirring was continued at the same temperature for 1 h. The resulting mixture was cannulated into a solution of 8 (1.5 g, 5.5 mmol) in THF (20 mL) at −78° C. The solution was maintained at −78° C. for 1 h, and then quenched with sat. aqueous NH4Cl and allowed to warm to room temperature. The organic layer was separated and then the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layer was washed with water, dried over Na2SO4, filtered, and evaporated under reduced pressure to give the crude product. The crude compound was purified by chromatography on silica gel to obtain the desired compound 9a (0.7 g, 42%). 1H NMR (CDCl3): δ 1.49 (s, 9H), 1.68-1.87 (m, 4H), 2.63 (s, 3H), 3.35 (m, 1H), 4.18 (br, 2H), 7.28 (d, J=8.4 Hz, 1H), 8.11 (dd, J=8.4, 2.1 Hz, 1H), 9.04 (d, J=2.1 Hz, 1H).

Workup

  1. customquenched with sat. aqueous NH4Cl
  2. temperatureto warm to room temperature
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
  5. washThe combined organic layer was washed with water
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto give the crude product
  10. customThe crude compound was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-e22983a898994fdc9aad5ca704266a5c
Source dataset
uspto-grants-2014_02
Patent number
US08658131B2

Reaction notes

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