2-Bromopyridine → HCID 71523148, compound

HRID 1620985Notes

Reaction equation

HRID 1620985 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[F:13][C:14]([F:28])([F:27])[C:15]1[N:20]=[CH:19][C:18]([C:21]2([CH:25]=[O:26])[CH2:24][CH2:23][CH2:22]2)=[CH:17][CH:16]=1.CCOC(C)=O>C1COCC1>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH:25]([C:21]1([C:18]2[CH:19]=[N:20][C:15]([C:14]([F:28])([F:13])[F:27])=[CH:16][CH:17]=2)[CH2:24][CH2:23][CH2:22]1)[OH:26]

Participants

6

Reactant 4

HCID 79732-BromopyridineHCID 8857Ethyl AcetateHCID 89524688HCID 89524688, compoundHCID 178418339Butyllithium

Product 1

HCID 71523148HCID 71523148, compoundYield 4.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To solution of 2-bromopyridine (506 mg, 3.2 mmol) in THF (10 mL) was added dropwise n-BuLi (2.4 mL, 3.84 mmol, 1.6 M) at −78° C. under nitrogen. After stirring for 30 minutes at −78° C., a solution of Example 85F (733 mg, 3.2 mmol) was added and the mixture was stirred for 30 minutes at the same temperature. The reaction mixture was allowed to warm up to room temperature, quenched with water (20 mL), extracted with dichloromethane (30 mL×2). The combined organic layers were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by Prep-TLC eluting with petroleum ether:EtOAc=2:1 to provide the title compound (45 mg, 4.6% yield) as a white solid. LC-MS: m/z 309.1 (M+H)+; 1H NMR (400 MHz, CDCl3): δ 8.30 (d, J=4.4 Hz, 1H), 8.07 (d, J=1.6 Hz, 1H), 7.57-7.61 (m, 1H), 7.46-7.49 (d, J=8.0 Hz, 1H), 7.34-7.39 (m, 1H), 7.14-7.17 (m, 1H), 7.04 (d, J=8.0 Hz, 1H), 5.05 (s, 1H), 4.51 (brs, 1H), 2.70-2.814 (m, 2H), 2.34-2.43 (m, 2H), 1.90-2.16 (m, 2H).

Workup

  1. stirringthe mixture was stirred for 30 minutes at the same temperature
  2. temperatureto warm up to room temperature
  3. customquenched with water (20 mL)
  4. extractionextracted with dichloromethane (30 mL×2)
  5. washThe combined organic layers were washed with water (10 mL) and brine (10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by Prep-TLC
  10. washeluting with petroleum ether

Sources & evidence

ORD record
ord-0cb9f5ec9f364e35986d4fde467a322a
Source dataset
uspto-grants-2014_07
Patent number
US08772500B2

Reaction notes

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