1,5-Dibromopentane → Ethyl 7-bromo-2-methyl-2-phenylheptanoate

HRID 239077

Reaction equation

HRID 239077 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[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][Br:28].[NH4+].[Cl-]>C1COCC1.CN1C(=O)N(C)CCC1>[Br:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][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 81001,5-DibromopentaneHCID 25517Ammonium ChlorideHCID 99643Benzeneacetic acid, alpha-methyl-, ethyl esterHCID 2724682Lithium diisopropylamide

Product 1

HCID 11313415Ethyl 7-bromo-2-methyl-2-phenylheptanoateYield 58%

Reagents, catalysts & solvents 2

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

Procedure

Under N2 atmosphere, a solution of LDA (2.0 M in heptane/THF/ethylbenzene, 1.85 mL, 3.70 mol) was added dropwise to a stirred solution of 202 (660 g, 3.70 mol) in anhydrous THF (6.6 L) over 30 min at −78° C. After 1 h, 1,5-dibromopentane (1390 g, 6.05 mol) was added, followed by the addition of DMPU (660 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 (24 L) and extracted with ethyl acetate (4×6.7 L). The combined organic layers were washed with brine (9 L), 1 N HCl (6 L), saturated aqueous NaHCO3 solution (6 L), and brine (6 L). The solution was dried over MgSO4 and concentrated in vacuo. The residue was distilled in high vacuo to yield 205h (700g, 58%) as a yellowish oil. Bp 140-145° C./0.3 mmHg. 1H NMR (CDCl3): δ 7.30-7.20 (m, 5 H), 4.09 (m, 2 H), 3.34 (t, 2 H, J=6.9), 2.05-1.80 (m, 4 H), 1.53 (s, 3 H), 1.43-1.14 (m, 4 H), 1.16 (t, 3 H, J=6.6). 13C NMR (CDCl3): δ 176.03, 143.99, 128.33, 126.60, 125.89, 60.68, 50.11, 39.03, 33.75, 32.51, 28.59, 23.93, 22.78, 14.10. HRMS (LSIMS, nba): Calcd for C16H24BrO2 (MH+): 327.0960, found: 327.0952. HPLC: 91.2% pure.

Workup

  1. stirringstirred overnight
  2. extractionextracted with ethyl acetate (4×6.7 L)
  3. washThe combined organic layers were washed with brine (9 L), 1 N HCl (6 L), saturated aqueous NaHCO3 solution (6 L), and brine (6 L)
  4. dry with materialThe solution was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. distillationThe residue was distilled in high vacuo

Sources & evidence

ORD record
ord-2e28450e03d84b6b89f1e861a08b4203
Source dataset
uspto-grants-2014_02
Patent number
US08642653B2

Linked notes

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