2-Bromopyridine → HCID 21306982, compound

HRID 713414Notes

Reaction equation

HRID 713414 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([C:26](=[O:31])N(OC)C)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>C1COCC1>[C:13]([O:17][C:18]([N:20]1[CH2:21][CH2:22][CH:23]([C:26]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)=[O:31])[CH2:24][CH2:25]1)=[O:19])([CH3:14])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 21306982HCID 21306982, compoundYield 35.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-bromopyridine (0.89 g, 5.62 mmol) in THF (10 mL) at −78° C. was added n-BuLi (2.81 mL, 1.6 M in THF, 5.62 mmol). The reaction was stirred for 30 minutes prior to the addition of 4-(methoxy-methyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (0.77 g, 2.81 mmol) as a solution in 5 mL of THF. The reaction was then stirred at room temperature for 30 minutes and then 1 hour at 60° C. The reaction was then quenched by adding a saturated solution of sodium bicarbonate and then extracted with 2×50 mL ethyl acetate. The combined organic layers was dried on magnesium sulfate and concentrated under vacuum to afford an orange oily solid which was purified via silica gel chromatography (gradient: ethyl acetate/hexane; 0:1 to 3:5) to afford the title compound as a white solid (290 mg). 1H NMR (400 MHz, CDC3) δ 8.70 (d, J=6.6 Hz, 1H), 8.05 (d, J=8.6 Hz, 1H), 7.86 (t, J=7.6 Hz, 1H), 7.46 (t, J=6.2 Hz, 1H), 4.25-4.13 (m, 2H), 4.09-4.00 (m, 1H), 2.94 (t, J=12.6 Hz, 2H), 1.91 (d, J=11.6 Hz, 2H), 1.69-1.65 (m, 2H), 1.50 (s, 9H). LRMS m/z ES+=290.8 (M+H), retention time 1.78.

Workup

  1. stirringThe reaction was then stirred at room temperature for 30 minutes
  2. custom1 hour
  3. customat 60° C
  4. customThe reaction was then quenched
  5. additionby adding a saturated solution of sodium bicarbonate
  6. extractionextracted with 2×50 mL ethyl acetate
  7. customThe combined organic layers was dried on magnesium sulfate
  8. concentrationconcentrated under vacuum
  9. customto afford an orange oily solid which
  10. customwas purified via silica gel chromatography (gradient: ethyl acetate/hexane; 0:1 to 3:5)

Sources & evidence

ORD record
ord-68a5372cf795474db37466de5094373f
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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