Hydrochloric Acid → ethyl 3-{2-fluoro-4-[(4-{[3-(4-fluorophenyl)-5-(2-phenylethyl)-1H-pyrazol-1-yl]methyl}benzyl)oxy]phenyl}propanoate

HRID 2110914Notes

Reaction equation

HRID 2110914 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH2:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[NH:10][N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[CH2:24][C:25]1[CH:46]=[CH:45][C:28]([CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[C:33]([F:44])[CH:32]=2)=[CH:27][CH:26]=1.Cl>CN(C)C=O>[F:44][C:33]1[CH:32]=[C:31]([O:30][CH2:29][C:28]2[CH:45]=[CH:46][C:25]([CH2:24][N:10]3[C:11]([CH2:13][CH2:14][C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)=[CH:12][C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[N:9]3)=[CH:26][CH:27]=2)[CH:36]=[CH:35][C:34]=1[CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 23143241Ethyl 3-(4-([4-(chloromethyl)benzyl]oxy}-2-fluorophenyl)propanoateHCID 231599063-(4-fluorophenyl)-5-(2-phenylethyl)-1H-pyrazole

Product 1

HCID 23159974ethyl 3-{2-fluoro-4-[(4-{[3-(4-fluorophenyl)-5-(2-phenylethyl)-1H-pyrazol-1-yl]methyl}benzyl)oxy]phenyl}propanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(4-fluorophenyl)-5-(2-phenylethyl)-1H-pyrazole (300 mg, 1.1 mmol) in N,N-dimethylformamide (5 mL) was added sodium hydride (60% in oil, 40 mg, 1.0 mmol) at 0° C., and the mixture was allowed to warm to room temperature and stirred for 30 min. Ethyl 3-(4-{[4-(chloromethyl)benzyl]oxy}-2-fluorophenyl)propanoate (350 mg, 1.0 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was poured into 1 N hydrochloric acid, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried using a Presep Dehydration tube (Manufactured by Wako Pure Chemical Industries, Ltd.), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1-1:1) to give the title compound as a yellow oil. 1H NMR (CDCl3) δ: 1.26 (3H, t, J=7.2 Hz), 2.56 (2H, t, J=7.6 Hz), 2.78-2.93 (6H, m), 4.12 (2H, q, J=7.2 Hz), 4.98 (2H, s), 5.24 (2H, s), 6.37 (1H, s), 6.59-6.68 (2H, m), 7.03-7.13 (7H, m), 7.19-7.37 (5H, m), 7.77 (2H, dd, J=9.0, 5.5 Hz).

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe ethyl acetate layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1-1:1)

Sources & evidence

ORD record
ord-15f92331e67b489fbcab4bc5a7ecd28d
Source dataset
uspto-grants-2009_04
Patent number
US07517910B2

Reaction notes

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