2-Fluoro-4-hydroxybenzaldehyde → HCID 18443678, compound

HRID 459258Notes

Reaction equation

HRID 459258 reaction equation
CC(C)([O-])C.[K+].[F:7][C:8]1[CH:15]=[C:14]([OH:16])[CH:13]=[CH:12][C:9]=1[CH:10]=[O:11].Br[CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:24][CH:23]=1>CN(C=O)C.O>[C:25]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:24]=[CH:23][C:22]([O:21][CH2:20][CH2:19][CH2:18][O:16][C:14]2[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[C:8]([F:7])[CH:15]=2)=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 5872462-Fluoro-4-hydroxybenzaldehydeHCID 152334631,1'-Biphenyl, 4-(3-bromopropoxy)-HCID 23665647Potassium tert-butoxide

Product 1

HCID 18443678HCID 18443678, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Potassium tert-butoxide (0.217 g, 1.93 mmol) was added to a solution of 2-fluoro-4-hydroxy-benzaldehyde (0.246 g, 1.76 mmol) in anhydrous DMF (5 mL) at 0° C., and the mixture was stirred for 30 min. 4-(3-Bromo-propoxy)-biphenyl (0.564 g, 1.93 mmol, Example 132, Step D) was added, and the mixture stirred at room temperature for 24 hours. The reaction mixture was diluted with water and extracted with EtOAc (5×15 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography (silica gel, hexanes/ethyl acetate 4:1) to give 4-[3-(biphenyl-4-yloxy)-propoxy]-2-fluoro-benzaldehyde as a white solid (540 mg, 88%). 1H NMR (200 MHz, CDCl3): δ 10.19 (s, 1H), 7.80 (t, 1H, J=8.4); 7.55–7.48 (m, 4H); 7.42–7.27 (m, 3H); 6.99–6.93 (m, 2H); 6.78 (dd, 1H, J=8.8, 2.6); 6.64 (dd, 1H, J=12.4, 2.2); 4.27–4.15 (m, 4H); 2.30 (qn, 2H, J=5.9)ppm.

Workup

  1. stirringthe mixture stirred at room temperature for 24 hours
  2. extractionextracted with EtOAc (5×15 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by silica gel chromatography (silica gel, hexanes/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-25416a84e3104dbbb1a1a74ceac57554
Source dataset
uspto-grants-2007_03
Patent number
US07192982B2

Reaction notes

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