Methyl iodide → Ethyl 5-bromo-2-methyl-2-phenyl-pentanoate

HRID 661165Notes

Reaction equation

HRID 661165 reaction equation
[C:1]1([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].[CH3:14]C([N-]C(C)C)C.CI.[Br:23][CH2:24][CH2:25][CH2:26]Br.[NH4+].[Cl-]>C1COCC1.CN1C(=O)N(C)CCC1>[Br:23][CH2:24][CH2:25][CH2:26][C:7]([CH3:14])([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 7590Ethyl phenylacetateHCID 80011,3-DibromopropaneHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamide

Product 1

HCID 23431358Ethyl 5-bromo-2-methyl-2-phenyl-pentanoateYield 113.9%

Reagents, catalysts & solvents 2

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

Procedure

Under Ar-atmosphere, to a solution of ethyl phenylacetate (42.4 g, 0.26 mol) and DMPU (5 mL) in THF (250 mL) was added dropwise a solution of LDA (2 M, 135 mL, 0.27 mol) at −78° C. The mixture was stirred for 2 h, before methyl iodide (41.40 g, 0.29 mol) was added in a single portion. The mixture was stirred overnight and allowed to warm to room temperature. After cooling to −78° C., 1,3-dibromopropane (72.7 g, 0.36 mol) was added and the mixture was allowed to stir overnight, gradually warming to room temperature. The mixture was hydrolyzed by consecutive addition of ice (200 g), saturated aqueous NH4Cl solution (400 mL), and coned HC (100 mL), and extracted with ethyl acetate (2×200 mL). The organic layers were dried over anhydrous MgSO4, and distilled under vacuum to give 205b as colorless oil (88.6 g, 59%). Bp 123-128° C./0.25 mmHg. 1H NMR (CDCl3): 7.20-7.10 (m, 5H), 4.12 (q, 2H, J=7.2), 3.35 (t, 2H, J=6.9), 2.18-2.00 (m, 2H), 1.77-1.72 (m, 2H), 1.56 (s, 3H), 1.18 (t, 3H, J=6.9). 13C NMR (CDCl3): 175.9, 143.4, 128.5, 126.9, 126.0, 61.0, 49.8, 38.2, 34.0, 28.5, 22.8, 14.2.

Workup

  1. additionwas added in a single portion
  2. temperatureAfter cooling to −78° C.
  3. stirringto stir overnight
  4. temperaturegradually warming to room temperature
  5. extractionextracted with ethyl acetate (2×200 mL)
  6. dry with materialThe organic layers were dried over anhydrous MgSO4
  7. distillationdistilled under vacuum

Sources & evidence

ORD record
ord-2c6e311ae6b643899efe28eb6a785c51
Source dataset
uspto-grants-2011_12
Patent number
US08084498B2

Reaction notes

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