Benzyl Bromide → HCID 118159323, compound

HRID 713216Notes

Reaction equation

HRID 713216 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[N:9][CH:10]=[CH:11][C:5]2=[N:4][C:3]=1[N:12]1[CH2:17][CH2:16][CH:15]([O:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])[CH2:14][CH2:13]1.[CH2:27](Br)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(#N)C>[CH2:27]([N:9]1[CH2:10][CH2:11][C:5]2[C:6](=[N:7][C:2]([Cl:1])=[C:3]([N:12]3[CH2:17][CH2:16][CH:15]([O:18][C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=4[F:26])[CH2:14][CH2:13]3)[N:4]=2)[CH2:8]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 5049666Sodium triacetoxyborohydrideHCID 90038500HCID 90038500, compound

Product 1

HCID 118159323HCID 118159323, compoundYield 56.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Benzyl bromide was purified by passage through a plug of basic alumina prior to use. A solution of 3-chloro-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)pyrido[3,4-b]pyrazine (736.2 mg, 1.954 mmol) in ACN (9.77 mL) was divided into two equal portions. Each solution was treated with a half portion of benzyl bromide (232 μL, 1.954 mmol) and stirred at 80° C. for 3 h. The reaction mixtures were allowed to cool to room temperature, and Each solution was treated with a half portion of sodium triacetoxyborohydride (1.242 g, 5.86 mmol). The reaction mixtures were stirred at room temperature for 1 h, then were quenched with saturated aqueous NaCl. The reaction mixtures were combined and partitioned between EtOAc with Et2O added to assist in phase separation and saturated aqueous NaCl. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography using a 20% to 60% gradient of EtOAc in heptanes gave the title compound (522.2 mg, 56.8%). ESI-MS m/z [M+H]+ 471.4.

Workup

  1. customBenzyl bromide was purified by passage through a plug of basic alumina
  2. customThe reaction mixtures
  3. temperatureto cool to room temperature
  4. customThe reaction mixtures
  5. stirringwere stirred at room temperature for 1 h
  6. customwere quenched with saturated aqueous NaCl
  7. customThe reaction mixtures
  8. custompartitioned between EtOAc with Et2O
  9. additionadded
  10. customto assist in phase separation and saturated aqueous NaCl
  11. dry with materialThe organic layer was dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-2f0a7ebad0be4df59849f20a787943d9
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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