Benzyl Bromide → HCID 59218761, compound

HRID 1468217Notes

Reaction equation

HRID 1468217 reaction equation
[Li+].CC([N-]C(C)C)C.C[C:10]1(C)[CH2:15][C:14]([CH3:17])([CH3:16])[CH2:13][CH2:12][C:11]1=[O:18].C(Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(=O)=[O:29].[CH:31]([OH:34])([CH3:33])C.[O:35]1CC[CH2:37][CH2:36]1>C(OCC)C>[CH2:17]([C:14]1([C:16]([O:34][CH2:31][CH3:33])=[O:29])[CH2:15][CH2:10][C:11]2([O:18][CH2:37][CH2:36][O:35]2)[CH2:12][CH2:13]1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 5

HCID 7498Benzyl BromideHCID 8028Tetrahydrofuran2×HCID 2724682Lithium diisopropylamideHCID 583881972,2,4,4-Tetramethylcyclohexan-1-oneHCID 86586944Isopropanol carbon dioxide

Product 1

HCID 59218761HCID 59218761, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

Under a nitrogen atmosphere, LDA (2M in THF/n-heptane/ethylbenzene, 20 mL, 40 mmol, 1.5 eq.) was added dropwise with stirring to a solution of 2 (5.8 g, 27 mmol) in dry tetrahydrofuran (THF, 60 mL) cooled to −78° C. in a dry ice/isopropanol bath. The mixture was allowed to slowly warm to room temperature over 20 minutes. The reaction mixture was again cooled to −78° C. and to it was added a solution of benzyl bromide (5.42 g, 32 mmol, 1.17 eq.) in dry THF (15 mL) using a syringe pump over 20 minutes. The reaction mixture was then stirred at −78° C. in the dry ice/isopropanol bath for 1 hour. After warming to room temperature, the mixture was diluted with ethyl ether (100 mL) and the organic layer was washed with saturated aqueous ammonium chloride solution (2×50 mL) and brine (1×50 mL) then dried over magnesium sulfate, filtered, and concentrated in vacuo to give a brown residue (14.9 g) as a crude. The crude product was purified by flash column chromatography [hexanes-ethyl acetate (4:1)] to give 25 (6.67 g, 81%) as an oil. 1H NMR (CDCl3) δ 7.28-7.18 (3H, m), 7.07-7.04 (2H, m), 4.08 (4H, q, J=7.1 Hz), 3.94 (4H, s), 2.83 (2H, s), 2.17-2.14 (2H, m), 1.72-1.53 (6H, m); 13C NMR (CDCl3) δ 175.5, 137.3, 130.0, 128.2, 126.8, 108.8, 64.5, 64.4, 60.5, 47.9, 46.7, 33.9, 32.3, 31.7, 26.5, 14.3; MS (ESI+) m/z 305.2 [M+H]+, HRMS (ESI+) calcd for C18H24O4+H 305.1753. found 305.1753.

Workup

  1. temperatureto slowly warm to room temperature over 20 minutes
  2. temperatureThe reaction mixture was again cooled to −78° C. and to it
  3. customover 20 minutes
  4. temperatureAfter warming to room temperature
  5. washthe organic layer was washed with saturated aqueous ammonium chloride solution (2×50 mL) and brine (1×50 mL)
  6. dry with materialthen dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3405746c24c84c84a248ca6a03885607
Source dataset
uspto-grants-2015_04
Patent number
US09000188B2

Reaction notes

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