3,4-Difluoro-2-[2-fluoro-4-(4-hydroxy-1-butynyl)anilino]-N-(2-hydroxyethoxy)benzamide → 3,4-difluoro-2-[2-fluoro-4-(4-hydroxybutyl)anilino]-N-(2-hydroxyethoxy)benzamide
Reaction equation
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH2:25][CH2:26][OH:27])=[CH:19][C:18]=2[F:28])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]>CCO.[Pd]>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][CH2:25][CH2:26][OH:27])=[CH:19][C:18]=2[F:28])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]Participants
Reactant 1
Product 1
Reagents, catalysts & solvents 2
Procedure
The product of Example 11, 3,4-Difluoro-2-[2-fluoro-4-(4-hydroxy-1-butynyl)anilino]-N-(2-hydroxyethoxy)-benzamide was hydrogenated in absolute EtOH in the presence of 5% Pd/C by the procedure of Example 1, Step D. Purification of the resulting oil was carried out by filtration through a plug of silica gel (EtOAc as eluant) to afford 3,4-difluoro-2-[2-fluoro-4-(4-hydroxybutyl)anilino]-N-(2-hydroxyethoxy)benzamide as a white crystalline solid (46%); m.p. (Et2O/EtOAc) 65-69° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.90 (br s, 1 H), 8.83 (br s, 1 H), 7.44–7.38 (m, 1 H), 7.13–7.07 (m, 1 H), 7.03 (dd, J=12.5, 1.6 Hz, 1 H), 6.88 (dd, J=8.2, 1.7 Hz, 1 H), 6.82 (ddd, J=8.7, 8.7, 4.3 Hz, 1 H), 4.76 (v br s, 1 H), 4.35 (t, J=5.2 Hz, 1H), 3.84 (t, J=4.8 Hz, 2 H), 3.56 (t, J=4.9 Hz, 2 H), 3.43–3.34 (m, 2 H), 2.55–2.47 (m, 2 H), 1.61–1.51 (m, 2 H), 1.46–1.37 (m, 2 H). Anal. calcd. for C19H21F3N2O4: C, 57.3; H, 5.3; N, 7.0. Found C, 57.4; H, 5.4; N, 6.9.
Workup
- customPurification of the resulting oil
- filtrationwas carried out by filtration through a plug of silica gel (EtOAc as eluant)
Sources & evidence
- ORD record
- ord-a3eb01a097864b2887c7d147dccbe10d
- Source dataset
- uspto-grants-2006_07
- Patent number
- US07078438B2
Reaction notes
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