4-Bromophenol → HCID 82094457, compound

HRID 718370Notes

Reaction equation

HRID 718370 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17]O)=[CH:12][CH:11]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:17][CH2:16][C:13]2[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 78084-BromophenolHCID 11776Triphenylphosphine2×HCID 820684-Fluorophenethyl AlcoholHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 82094457HCID 82094457, compoundYield 99.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-bromophenol (81.7 g, 472 mmol), 2-(4-fluorophenyl)ethanol (79 g, 567 mmol) and Ph3P (149 g, 567 mmol) in THF (100 mL) cooled in an ice-water bath was added drop wise DEAD (93 ml, 590 mmol) over 20 min. Note: The reaction is exothermic and efficient cooling is highly recommended before initiating large scale reaction. After 1 h, cold bath was removed and stirred overnight (17 h) at rt. Then, the reaction mixture was concentrated, the resulting residue triturated with hexanes, filtered and the filter cake washed with 10% ether/hexanes (2-lit). The filtrate was concentrated and purified by flash chromatography (silica gel column 3″×11″) using 4-lit hexanes and 2-lit 2% EtOAc/Hex to afford 1-bromo-4-(4-fluorophenethoxy)benzene (142 g, 469 mmol, 99% yield) as colorless liquid (contaminated with ˜2.5% Ph3P by 1HNMR). 1H NMR (500 MHz, CDCl3) δ 7.41-7.36 (m, 2H), 7.28-7.22 (m, 2H), 7.05-6.99 (m, 2H), 6.82-6.76 (m, 2H), 4.14 (t, J=6.9 Hz, 2H), 3.08 (t, J=6.9 Hz, 2H).

Workup

  1. temperatureefficient cooling
  2. customscale reaction
  3. customcold bath was removed
  4. concentrationThen, the reaction mixture was concentrated
  5. customthe resulting residue triturated with hexanes
  6. filtrationfiltered
  7. washthe filter cake washed with 10% ether/hexanes (2-lit)
  8. concentrationThe filtrate was concentrated
  9. custompurified by flash chromatography (silica gel column 3″×11″)

Sources & evidence

ORD record
ord-d55b9f9fa4f04a8e8d8b8da94a414d41
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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