Hydrogen Bromide → 2-Bromo-1-(4-(dibenzylamino)-2-methylcyclopentyl)ethanone

HRID 1969830Notes

Reaction equation

HRID 1969830 reaction equation
[C:1](Cl)(=O)C(Cl)=O.[CH2:7]([N:14]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH:15]1[CH2:19][CH:18]([C:20](O)=[O:21])[CH:17]([CH3:23])[CH2:16]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.CN(C=O)C.C[Si](C=[N+]=[N-])(C)C.[BrH:43].C([O-])(O)=O.[Na+]>C(Cl)Cl.C1COCC1.CC#N>[Br:43][CH2:1][C:20]([CH:18]1[CH2:19][CH:15]([N:14]([CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:16][CH:17]1[CH3:23])=[O:21]

Participants

10

Reactant 6

HCID 260Hydrogen BromideHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 167693TrimethylsilyldiazomethaneHCID 516892Sodium BicarbonateHCID 585575354-(Dibenzylamino)-2-methylcyclopentanecarboxylic acid

Product 1

HCID 585571452-Bromo-1-(4-(dibenzylamino)-2-methylcyclopentyl)ethanoneYield 69.3%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Oxalyl chloride (4.37 mL, 49.9 mmol) was slowly added to a solution of 4-(dibenzylamino)-2-methylcyclopentanecarboxylic acid (7.34 g, 22.7 mmol) in DCM (100 mL), (note: mild gas evolution) followed by a dropwise addition of DMF (0.26 mL, 3.41 mmol). The mixture was stirred at ambient temperature for about 14 h. The solvent was removed under reduced pressure to yield a beige amorphous solid, which was dissolved in THF and MeCN (1:1, 100 mL). The resulting solution was added to a solution of trimethylsilyldiazomethane (2 M in Et2O, 39.7 mL, 79 mmol) in THF and MeCN (1:1, 100 mL) at about 0° C. The resulting mixture was stirred at about 0° C. for about 3 h and then was quenched by a dropwise addition of HBr (48% aqueous, 25 mL, 221 mmol). The resulting mixture was neutralized by a dropwise addition of saturated aqueous NaHCO3 (300 mL) and the layers were separated. The organic layer was dried over anhydrous MgSO4 and concd under reduced pressure. The residue was purified by silica gel chromatography eluting with 5% to 45% of EtOAc in heptane to yield 2-bromo-1-(4-(dibenzylamino)-2-methylcyclopentyl)ethanone (6.3 g, 69%) as a yellow oil: LC/MS (Table 1, Method a) Rt=2.90 min; MS m/z 400, 402 (M+H)+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto yield a beige amorphous solid, which
  3. stirringThe resulting mixture was stirred at about 0° C. for about 3 h
  4. customthe layers were separated
  5. dry with materialThe organic layer was dried over anhydrous MgSO4 and concd under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 5% to 45% of EtOAc in heptane

Sources & evidence

ORD record
ord-ecd222bf6dfa41389ff3681b350cf18b
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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