Benzyl Bromide → HCID 69953258, compound

HRID 2301194Notes

Reaction equation

HRID 2301194 reaction equation
F[C:2](F)(F)[S:3]([O:6][Si](C)(C)C)(=O)=[O:4].N1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[N:19]1[C:24]([CH3:25])=[CH:23][CH:22]=[CH:21][C:20]=1[CH3:26].[C:27](=[O:30])([OH:29])[O-:28].[Na+].[CH2:32]([N:34]([CH2:37][CH3:38])[CH2:35][CH3:36])[CH3:33].C(Br)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42]C=1.[CH2:47]1[CH2:51][O:50]C[CH2:48]1>C(Cl)Cl.CN(C=O)C>[CH:14]1[C:2]([S:3]([NH2:19])(=[O:6])=[O:4])=[CH:18][CH:17]=[CH:16][CH:15]=1.[C:51]([OH:50])(=[O:4])/[CH:47]=[CH:48]/[C:27]([OH:29])=[O:30].[C:33]1([CH2:32][N:34]2[CH2:37][CH2:38][CH:17]([CH2:18][CH2:25][C:24]3[C:23]4[CH:22]=[CH:21][CH:20]=[CH:26][C:27]=4[O:28][N:19]=3)[CH2:36][CH2:35]2)[CH:42]=[CH:43][CH:44]=[CH:45][CH:40]=1

Participants

10

Reactant 7

HCID 7498Benzyl BromideHCID 79372,6-LutidineHCID 8028TetrahydrofuranHCID 8082PiperidineHCID 8471TriethylamineHCID 65367Trimethylsilyl triflateHCID 516892Sodium Bicarbonate

Product 1

HCID 69953258HCID 69953258, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Trimethylsilyl trifluoromethanesulfonate (1.30 mL, 6.76 mmol) was added dropwise to a cold (0° C.) solution of the piperidine formed in step b (0.819 g, 1.69 mmol) and 2,6-lutidine (0.590 mL, 5.07 mmol) in CH2Cl2 (17 mL). After 1.5 hours, saturated sodium bicarbonate (NaHCO3) was added and the resulting mixture was stirred at room temperature for 15 min. The white precipitate formed was collected by filtration and redissolved in water at pH 2. This acidic aqueous layer was extracted with CH2Cl2 (2 times) and EtOAc (1 time). All organic layers were combined, dried (MgSO4), filtered, and concentrated. The crude white solid obtained was suspended in THF (30 mL) and DMF (50 mL), and triethylamine (0.40 mL, 2.86 mmol) and benzyl bromide (0.22 mL, 1.86 mmol) were added. The resulting heterogenous mixture was stirred at room temperature for 24 hours (with time a more homogenous mixture was obtained). The mixture was concentrated, and CH2Cl2 was added to the residue. The organic layer was washed with water and brine and dried (MgSO4), filtered, and concentrated. Purification by silica gel flash chromatography (CH2Cl2→5% MeOH/CH2Cl2) gave the title compound (free base) (0.334 g, 49%) as a white foam.

Workup

  1. customThe white precipitate formed
  2. filtrationwas collected by filtration
  3. dissolutionredissolved in water at pH 2
  4. extractionThis acidic aqueous layer was extracted with CH2Cl2 (2 times) and EtOAc (1 time)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude white solid obtained
  9. stirringThe resulting heterogenous mixture was stirred at room temperature for 24 hours (with time a more homogenous mixture
  10. customwas obtained)
  11. concentrationThe mixture was concentrated
  12. additionCH2Cl2 was added to the residue
  13. washThe organic layer was washed with water and brine
  14. dry with materialdried (MgSO4)
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customPurification by silica gel flash chromatography (CH2Cl2→5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-55fdf4feabc54198bd15c430bceab092
Source dataset
uspto-grants-2002_12
Patent number
US06498255B2

Reaction notes

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