1,4-Dibromobutane → Ethyl 6-bromo-2-methyl-2-phenylhexanoate

HRID 873289Notes

Reaction equation

HRID 873289 reaction equation
[Li+].CC([N-]C(C)C)C.[CH2:9]([O:11][C:12](=[O:21])[CH:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:14])[CH3:10].[Br:22][CH2:23][CH2:24][CH2:25][CH2:26]Br.[NH4+].[Cl-]>C1COCC1.CN1C(=O)N(C)CCC1>[Br:22][CH2:23][CH2:24][CH2:25][CH2:26][C:13]([CH3:14])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:12]([O:11][CH2:9][CH3:10])=[O:21]

Participants

7

Reactant 4

HCID 80561,4-DibromobutaneHCID 25517Ammonium ChlorideHCID 99643Benzeneacetic acid, alpha-methyl-, ethyl esterHCID 2724682Lithium diisopropylamide

Product 1

HCID 11174430Ethyl 6-bromo-2-methyl-2-phenylhexanoateYield 99%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

A solution of LDA (14 mL, 28 mmol, 2.0 M in heptane) was added dropwise to a stirred solution of 202 (5.0 g, 28.06 mmol) in anhydrous THF (50 mL) at −78° C. After 1 h, the reaction mixture was added to a −78° C. cold solution of 1,4-dibromobutane (10.06 g, 23.1 mmol) in THF. After the addition of DMPU (5 mL), the reaction mixture was stirred for 1 h, then warmed to room temperature and stirred overnight. The mixture was poured into saturated aqueous NH4Cl solution (500 mL) and extracted with ethyl acetate (4×100 mL). The combined organic phases were washed with brine (100 mL), 1 M HCl (50 mL), saturated aqueous NaHCO3 solution (50 mL), and brine (100 mL). The solution was dried over anhydrous MgSO4 and concentrated in vacuo. The residue was distilled to give 205d as an oil (7.16 g, 99%). Bp 130-131° C./0.2 mm Hg. 1H NMR (CDCl3), δ (ppm): 7.40-7.15 (m, 5H), 4.13 (q, 2H, J=6.7), 3.36 (t, 2H, J=6.7), 2.02 (m, 2H), 1.86 (m, 2H), 1.56 (s, 3H), 1.34 (m, 2H), 1.18 (t, 3H, J=6.7). 13C NMR (CDCl3), δ (ppm): 176.13, 143.91, 128.51, 126.81, 126.03, 60.93, 50.22, 38.53, 33.56, 33.30, 23.58, 22.77, 14.22. HRMS (FAB): Calcd for C15H2179BrO2 (MH+): 313.0803, found 313.0786.

Workup

  1. stirringstirred overnight
  2. extractionextracted with ethyl acetate (4×100 mL)
  3. washThe combined organic phases were washed with brine (100 mL), 1 M HCl (50 mL), saturated aqueous NaHCO3 solution (50 mL), and brine (100 mL)
  4. dry with materialThe solution was dried over anhydrous MgSO4
  5. concentrationconcentrated in vacuo
  6. distillationThe residue was distilled

Sources & evidence

ORD record
ord-6e097e0a7d604f0f91d84966ee71691f
Source dataset
uspto-grants-2015_03
Patent number
US08975300B2

Reaction notes

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