Diethyl Ether → HCID 66678440, compound

HRID 2410565Notes

Reaction equation

HRID 2410565 reaction equation
[CH3:1][Li].C[CH2:4][O:5][CH2:6][CH3:7].[Br:8][C:9]1[CH:10]=C(C=O)[C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[CH:13][CH:14]=1.IC>C1COCC1>[CH3:4][O:5][CH:6]([C:7]1[CH:10]=[C:9]([Br:8])[CH:14]=[CH:13][C:12]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH3:21])[CH3:1]

Participants

6

Reactant 4

HCID 3283Diethyl Ether2×HCID 6328Methyl iodideHCID 12834670HCID 12834670, compoundHCID 178418348HCID 178418348, compound2×

Product 1

HCID 66678440HCID 66678440, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of methyllithium in Et2O (1.6M, 6.8 mL, 10.9 mmol) was added dropwise into a solution of 4-bromo-2′-methylbiphenyl-2-carbaldehyde (2.0 g, 7.3 mmol) in anhydrous THF (30 mL) cooled at −78° C. under nitrogen atmosphere. The resulting mixture was stirred at −78° C. for 45 minutes and an additional amount of methyllithium in Et2O (1.6M, 3.4 mL, 5.5 mmol) was added. After 10 minutes, iodomethane (4.1 ml, 65.4 mmol) was added. The cooling bath was removed and the reaction mixture was stirred at RT for 5 days. The reaction mixture was diluted with MTBE (100 mL), and then washed with water (2×50 mL) and brine (50 mL). The aqueous layers were extracted with MTBE (100 mL). The organic layers were combined, dried (MgSO4) and concentrated under vacuum. After purification by flash chromatography (silica, heptane/MTBE), the title compound was obtained as a pale yellow oil (1.90 g, 86%). HPLC (Method A) Rt 5.7 min (Purity: 91%). 1H NMR (DMSO-d6, 300 MHz) δ 7.62 (d, J=2.2 Hz, 0.4H), 7.59 (d, J=2.2 Hz, 0.6H), 7.52 (dd, J=8.1, 2.2 Hz, 1H), 7.35-7.21 (m, 3H), 7.13-7.02 (m, 2H), 4.05 (q, J=6.4 Hz, 0.4H), 3.84 (q, J=6.4 Hz, 0.6H), 3.05 (s, 1.2H), 3.03 (s, 1.8H), 2.03 (s, 1.8H), 1.98 (s, 1.2H), 1.17 (d, J=6.4 Hz, 1.8H), 1.11 (d, J=6.4 Hz, 1.2H).

Workup

  1. waitAfter 10 minutes
  2. customThe cooling bath was removed
  3. stirringthe reaction mixture was stirred at RT for 5 days
  4. additionThe reaction mixture was diluted with MTBE (100 mL)
  5. washwashed with water (2×50 mL) and brine (50 mL)
  6. extractionThe aqueous layers were extracted with MTBE (100 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under vacuum
  9. customAfter purification by flash chromatography (silica, heptane/MTBE)

Sources & evidence

ORD record
ord-c818664b570b4a1d9acfc8118e6ff4bd
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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