1,1'-Biphenyl, 4-(3-bromopropoxy)- → 3-{4-[3-(Biphenyl-4-yloxy)-propoxy]-3-fluoromethyl-phenyl}-2-methoxy-acrylic acid methyl ester

HRID 459162Notes

Reaction equation

HRID 459162 reaction equation
CC(C)([O-])C.[K+].[CH3:7][O:8][C:9](=[O:25])[C:10]([O:23][CH3:24])=[CH:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([C:19]([F:22])(F)F)[CH:13]=1.Br[CH2:27][CH2:28][CH2:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:33][CH:32]=1>CN(C)C=O>[CH3:7][O:8][C:9](=[O:25])[C:10]([O:23][CH3:24])=[CH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:27][CH2:28][CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:33][CH:32]=2)=[C:14]([CH2:19][F:22])[CH:13]=1

Participants

5

Reactant 3

HCID 152334631,1'-Biphenyl, 4-(3-bromopropoxy)-HCID 23665647Potassium tert-butoxideHCID 694212063-(4-Hydroxy-3-trifluoromethyl-phenyl)-2-methoxy-acrylic acid methyl ester

Product 1

HCID 694281953-{4-[3-(Biphenyl-4-yloxy)-propoxy]-3-fluoromethyl-phenyl}-2-methoxy-acrylic acid methyl esterYield 61.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium tert-butoxide (15 mg, 0.13 mmol) was added at 0° C. to a solution of 3-(4-hydroxy-3-trifluoromethyl-phenyl)-2-methoxy-acrylic acid methyl ester (35 mg, 0.126 mmol) in dry N,N-dimethylformamide (0.6 mL). The mixture was stirred for 0.5 hours and 4-(3-Bromo-propoxy)-biphenyl (example 23, Step D) (45 mg, 0.15 mmol) was added. The reaction was stirred for 6 hours at room temperature and quenched with a saturated solution of ammonium chloride (10 mL). The aqueous layer was separated and extracted with methylene chloride (5×10 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated under vacuum. The residue was chromatographed (silica gel, hexanes/ethyl acetate 8:2) to produce 3-{4-[3-(biphenyl-4-yloxy)-propoxy]-3-fluoromethyl-phenyl}-2-methoxy-acrylic acid methyl ester as a colorless oil (35 mg, 57%). 1H-NMR (CDCl3, 200.15 MHz): δ 8.00 (d, 1H, J=1.6), 7.89 (dd, 1H, J=8.6, 1.6), 7.46–7.26 (m, 7H), 7.05–6.93 (m, 4H), 4.33–4.20 (m, 4H), 3.86 (s, 3H), 3.79 (s, 3H), 2.33 (qn, 2H, J=5.9).

Workup

  1. stirringThe reaction was stirred for 6 hours at room temperature
  2. customquenched with a saturated solution of ammonium chloride (10 mL)
  3. customThe aqueous layer was separated
  4. extractionextracted with methylene chloride (5×10 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was chromatographed (silica gel, hexanes/ethyl acetate 8:2)

Sources & evidence

ORD record
ord-e8721f6fd2914f708b3d80e378dad402
Source dataset
uspto-grants-2007_03
Patent number
US07192982B2

Reaction notes

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