3-Fluoro-4-hydroxybenzaldehyde → 4-[3-(Biphenyl-4-yloxy)-propoxy]-3-fluoro-benzaldehyde

HRID 459159Notes

Reaction equation

HRID 459159 reaction equation
CC(C)([O-])C.[K+].[F:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[OH:16])[CH:11]=[O:12].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)C=O.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:15]2[CH:14]=[CH:13][C:10]([CH:11]=[O:12])=[CH:9][C:8]=2[F:7])=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 5872503-Fluoro-4-hydroxybenzaldehydeHCID 152334631,1'-Biphenyl, 4-(3-bromopropoxy)-HCID 23665647Potassium tert-butoxide

Product 1

HCID 184436794-[3-(Biphenyl-4-yloxy)-propoxy]-3-fluoro-benzaldehydeYield 83.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Potassium tert-butoxide (198 mg, 1.76 mmol) was added, at 0° C., to a solution of 3-Fluoro-4-hydroxy-benzaldehyde (235 mg, 1.68 mmol) in dry N,N-dimethylformamide (2 mL). The mixture was stirred for 10 minutes. 4-(3-Bromo-propoxy)-biphenyl (example 23, Step D) (539 mg, 1.84 mmol) was added and the reaction was stirred for 24 hours at room temperature. The mixture was diluted with water (15 mL) and extracted with ethyl acetate (4×15 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated under vacuum to produce a solid which was washed with hexanes to produce 4-[3-(Biphenyl-4-yloxy)-propoxy]-3-fluoro-benzaldehyde as a pale brown solid (490 mg, 83%). 1H-NMR (CDCl3, 200.15 MHz): δ 9.83 (d, 1H, J=2.2), 7.64–7.23 (m, 9H), 7.09 (t, 1H, J=8.2), 6.96 (d, 2H, J=8.8), 4.32 (t, 2H, J=5.9), 4.21 (t, 2H, J=5.9), 2.35 (qn, 2H, J=5.9).

Workup

  1. stirringthe reaction was stirred for 24 hours at room temperature
  2. extractionextracted with ethyl acetate (4×15 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customto produce a solid which
  7. washwas washed with hexanes

Sources & evidence

ORD record
ord-d0726478f142444396bab02c57ecc530
Source dataset
uspto-grants-2007_03
Patent number
US07192982B2

Reaction notes

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