Cyclooctanone → HCID 59511109, compound

HRID 1774259Notes

Reaction equation

HRID 1774259 reaction equation
[C:1]1(=[O:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].CC([N-]C(C)C)C.Br[CH2:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=1>C1COCC1>[CH3:27][O:26][C:24](=[O:25])[C:23]1[CH:28]=[CH:29][C:20]([CH2:19][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:1]2=[O:9])=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 10403CyclooctanoneHCID 256687Methyl 4-(bromomethyl)benzoateHCID 2724682Lithium diisopropylamide

Product 1

HCID 59511109HCID 59511109, compoundYield 80.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring solution of cyclooctanone (1.76 g, 14.0 mmol) in THF (30 mL) at −78° C. was added LDA (8.54 mL, 15.4 mmol, 1.8 M in heptane/THF/ethylbenzene). After 1 h, a solution of methyl 4-bromomethylbenzoate (3.53 g, 15.4 mmol) in THF (10 mL) was added and the reaction mixture was allowed to warm to rt. After 30 min, the reaction was quenched with H2O (10 mL) and the THF was removed on a rotary evaporator. The residue was diluted with EtOAc (100 mL), washed with H2O (3×100 mL) and brine (1×50 mL), and dried over MgSO4. Chromatography of the crude product (50:1 to 9:1 hexanes/EtOAc) yielded the desired product as a colorless oil (3.08 g, 80%, Rf=0.30, 9:1 hexanes/EtOAc). IR: 3426, 2929, 2856, 1721, 1700, 1657, 1611 cm−1. 1H NMR (CDCl3, 300 MHz): δ 1.10-1.28 (m, 1H), 1.28-1.42 (m, 1H), 1.42-1.80 (m, 6H), 1.80-1.90 (m, 1H), 1.90-2.08 (m, 1H), 2.08-2.18 (m, 1H), 2.22-2.35 (m, 1H), 2.64 (dd, 1H, J=12.6, 6.0 Hz), 3.01 (m, 2H), 3.89 (s, 3H), 7.20 (d, 2H, J=8.1 Hz), 7.93 (d, 2H, J=8.4 Hz). 13C NMR (CDCl3, 75 MHz): δ 24.5, 24.6, 25.1, 27.7, 32.9, 38.1, 43.2, 51.5, 52.0, 128.1, 129.0, 129.7, 145.6, 167.0, 218.9. FAB-HRMS: Calcd. for C17H23O3+ [M+H]+: 275.1647. found: 275.1648.

Workup

  1. waitAfter 30 min
  2. customthe reaction was quenched with H2O (10 mL)
  3. customthe THF was removed on a rotary evaporator
  4. additionThe residue was diluted with EtOAc (100 mL)
  5. washwashed with H2O (3×100 mL) and brine (1×50 mL)
  6. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-c7e74def19ad4fc58915d0bf34112663
Source dataset
uspto-grants-2016_02
Patent number
US09260371B2

Reaction notes

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